Datasets:

kenza-ily

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JAMA_Chen2024_G

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https://jamanetwork.com/journals/jamadermatology/fullarticle/2811083

A man in his 30s with AIDS presented with acute-onset painful scattered umbilicated papulopustules and ovoid ulcerated plaques with elevated, pink borders on the face, trunk, and extremities (Figure, A). The patient also had a new-onset cough but was afebrile and denied other systemic symptoms. Due to his significant immunocompromise, the clinical presentation was highly suspicious for infection. For rapid bedside differentiation of multiple infectious etiologies, a Tzanck smear was performed by scraping the base of an ulcerated lesion and inner aspect of a pseudopustule and scraping its base with a #15 blade. These contents were placed on a glass slide, fixed, and stained with Wright-Giemsa and subsequently Papanicolaou staining to further characterize the changes seen.A, Clinical image demonstrating papulopustules and ovoid ulcerated plaques with elevated, pink borders on the elbows. B, Tzanck smear using Wright-Giemsa staining of specimen demonstrating ballooning of keratinocytes and peripheralization of nuclear material (original magnification ×20). What Is Your Diagnosis?

Herpes simplex virus

Histoplasmosis

Molluscum contagiosum

Mpox

D. Mpox

D

Mpox

The photographs demonstrate a Tzanck smear using Wright-Giemsa stain (Figure, B) with large ballooning keratinocytes with peripheral nuclear staining seen in a patient with subsequently polymerase chain reaction (PCR)-confirmed mpox. Mpox is a member of the pox virus family, which presents with nonspecific symptoms such as fever followed by characteristic skin changes including macules, papules, vesicles, and pustules progressing with cephalocaudal spread or in the genital and/or gluteal region in the most recent outbreak. On histopathologic findings, mpox features vary depending on the stage of the lesion.1,2 Early lesions tend to demonstrate ballooning degeneration, whereas later lesions have few viable keratinocytes.2 The viral cytopathic changes, most often seen in pseudopustular lesions, include multinucleated keratinocytes with ground glass appearance and nuclear contents pushed to the periphery, resulting in a basophilic halo.2 The lack of a true pustule with collections of neutrophils in the stratum corneum have led some to describe these lesions as pseudopustular.Tzanck smear is an inexpensive, rapid, and simple technique to perform cytologic analysis from skin. Initially described in 1947 by Arnault Tzanck for diagnosing vesiculobullous disorders, it is commonly used in diagnosing herpetic infections, which have characteristic features of acantholysis, acute inflammation, and keratinocytic ballooning and specific nuclear changes of molding, multinucleation, and chromatin margination.3 The findings of acantholysis and nuclear cytopathic changes are similarly seen in histopathologic examination of herpes simplex virus (HSV). Herpetic infections may present with clustered vesicles with a pink inflammatory rim, although more verrucous lesions have been described in immunosuppressed patients.In the Tzanck smear from a lesion of mpox in this patient (Figure, B), enlarged keratinocytes were seen with expanded cytoplasm and nuclear material pushed to the periphery, and the nuclear changes associated with HSV were all absent. The observed difference in cytologic features including the nuclear material rimming or pushed to the periphery of the cells is due to the location of viral replication; herpes viruses replicate in the nucleus, whereas mpox replicates in the cytoplasm.4 Although not part of routine practice, Papanicolaou staining was performed in this case to confirm infected cells and provide additional nuclear detail because Tzanck smears in patients with mpox were not previously reported. The findings highlighted the peripheralization of nuclear material in cells with eosinophilic staining, confirming the keratinocyte origin to the cells. A background inflammatory infiltrate was noted and can be seen in most infections.Tzanck smear can also be used to diagnose other viral and fungal infections. Molluscum contagiosum, which presents with multiple umbilicated papules, demonstrates the characteristic large (30-40 µm) ovoid homogenous basophilic staining keratinocytes called Henderson-Patterson bodies that correspond to the identically named intracytoplasmic inclusions seen on histopathologic findings.5,6 Using bedside diagnostics (including Wright Giemsa staining), blastomycosis is diagnosed with 8- to 15-µm spores with broad-based budding, similar in appearance to the organism in histologic examination.5 Histoplasmosis has small (2 to 3 µm) intracellular organisms in macrophages with artifactual clearing (pseudocapsule).5 Both of these fungal infections may manifest clinically as nonhealing ulcerations, verrucous plaques, or multiple papules or nodules and can histologically demonstrate pseudoepitheliomatous hyperplasia with characteristic organisms. The use of the Tzanck smear in diagnosis of any infection depends on the timing of the lesion and is most sensitive with vesicular or pustular lesions.6 Although we only tested 1 stage of lesions, we hypothesize this test will similarly be more sensitive for earlier lesions in patients with mpox.Tzanck smear is a useful technique that can be used to differentiate mpox from other infections at the bedside or in remote settings where PCR or additional culture techniques are not easily accessible. Infection prevention and control precautions are important to help prevent additional spread of this virus with sharp injuries, and caution with unroofing of the lesions is critical to avoid additional spread.7 Knowledge of the cytologic differences of mpox compared with other viral infections is important in the early recognition, diagnosis, and treatment of these patients.

Dermatology

A man in his 30s with AIDS presented with acute-onset painful scattered umbilicated papulopustules and ovoid ulcerated plaques with elevated, pink borders on the face, trunk, and extremities (Figure, A). The patient also had a new-onset cough but was afebrile and denied other systemic symptoms. Due to his significant immunocompromise, the clinical presentation was highly suspicious for infection. For rapid bedside differentiation of multiple infectious etiologies, a Tzanck smear was performed by scraping the base of an ulcerated lesion and inner aspect of a pseudopustule and scraping its base with a #15 blade. These contents were placed on a glass slide, fixed, and stained with Wright-Giemsa and subsequently Papanicolaou staining to further characterize the changes seen.A, Clinical image demonstrating papulopustules and ovoid ulcerated plaques with elevated, pink borders on the elbows. B, Tzanck smear using Wright-Giemsa staining of specimen demonstrating ballooning of keratinocytes and peripheralization of nuclear material (original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Herpes simplex virus

Mpox

Histoplasmosis

Molluscum contagiosum

b

male

31-40

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2811083

A man in his 30s with AIDS presented with acute-onset painful scattered umbilicated papulopustules and ovoid ulcerated plaques with elevated, pink borders on the face, trunk, and extremities (Figure, A). The patient also had a new-onset cough but was afebrile and denied other systemic symptoms. Due to his significant immunocompromise, the clinical presentation was highly suspicious for infection. For rapid bedside differentiation of multiple infectious etiologies, a Tzanck smear was performed by scraping the base of an ulcerated lesion and inner aspect of a pseudopustule and scraping its base with a #15 blade. These contents were placed on a glass slide, fixed, and stained with Wright-Giemsa and subsequently Papanicolaou staining to further characterize the changes seen.A, Clinical image demonstrating papulopustules and ovoid ulcerated plaques with elevated, pink borders on the elbows. B, Tzanck smear using Wright-Giemsa staining of specimen demonstrating ballooning of keratinocytes and peripheralization of nuclear material (original magnification ×20). What Is Your Diagnosis?

Herpes simplex virus

Histoplasmosis

Molluscum contagiosum

Mpox

D. Mpox

D

Mpox

The photographs demonstrate a Tzanck smear using Wright-Giemsa stain (Figure, B) with large ballooning keratinocytes with peripheral nuclear staining seen in a patient with subsequently polymerase chain reaction (PCR)-confirmed mpox. Mpox is a member of the pox virus family, which presents with nonspecific symptoms such as fever followed by characteristic skin changes including macules, papules, vesicles, and pustules progressing with cephalocaudal spread or in the genital and/or gluteal region in the most recent outbreak. On histopathologic findings, mpox features vary depending on the stage of the lesion.1,2 Early lesions tend to demonstrate ballooning degeneration, whereas later lesions have few viable keratinocytes.2 The viral cytopathic changes, most often seen in pseudopustular lesions, include multinucleated keratinocytes with ground glass appearance and nuclear contents pushed to the periphery, resulting in a basophilic halo.2 The lack of a true pustule with collections of neutrophils in the stratum corneum have led some to describe these lesions as pseudopustular.Tzanck smear is an inexpensive, rapid, and simple technique to perform cytologic analysis from skin. Initially described in 1947 by Arnault Tzanck for diagnosing vesiculobullous disorders, it is commonly used in diagnosing herpetic infections, which have characteristic features of acantholysis, acute inflammation, and keratinocytic ballooning and specific nuclear changes of molding, multinucleation, and chromatin margination.3 The findings of acantholysis and nuclear cytopathic changes are similarly seen in histopathologic examination of herpes simplex virus (HSV). Herpetic infections may present with clustered vesicles with a pink inflammatory rim, although more verrucous lesions have been described in immunosuppressed patients.In the Tzanck smear from a lesion of mpox in this patient (Figure, B), enlarged keratinocytes were seen with expanded cytoplasm and nuclear material pushed to the periphery, and the nuclear changes associated with HSV were all absent. The observed difference in cytologic features including the nuclear material rimming or pushed to the periphery of the cells is due to the location of viral replication; herpes viruses replicate in the nucleus, whereas mpox replicates in the cytoplasm.4 Although not part of routine practice, Papanicolaou staining was performed in this case to confirm infected cells and provide additional nuclear detail because Tzanck smears in patients with mpox were not previously reported. The findings highlighted the peripheralization of nuclear material in cells with eosinophilic staining, confirming the keratinocyte origin to the cells. A background inflammatory infiltrate was noted and can be seen in most infections.Tzanck smear can also be used to diagnose other viral and fungal infections. Molluscum contagiosum, which presents with multiple umbilicated papules, demonstrates the characteristic large (30-40 µm) ovoid homogenous basophilic staining keratinocytes called Henderson-Patterson bodies that correspond to the identically named intracytoplasmic inclusions seen on histopathologic findings.5,6 Using bedside diagnostics (including Wright Giemsa staining), blastomycosis is diagnosed with 8- to 15-µm spores with broad-based budding, similar in appearance to the organism in histologic examination.5 Histoplasmosis has small (2 to 3 µm) intracellular organisms in macrophages with artifactual clearing (pseudocapsule).5 Both of these fungal infections may manifest clinically as nonhealing ulcerations, verrucous plaques, or multiple papules or nodules and can histologically demonstrate pseudoepitheliomatous hyperplasia with characteristic organisms. The use of the Tzanck smear in diagnosis of any infection depends on the timing of the lesion and is most sensitive with vesicular or pustular lesions.6 Although we only tested 1 stage of lesions, we hypothesize this test will similarly be more sensitive for earlier lesions in patients with mpox.Tzanck smear is a useful technique that can be used to differentiate mpox from other infections at the bedside or in remote settings where PCR or additional culture techniques are not easily accessible. Infection prevention and control precautions are important to help prevent additional spread of this virus with sharp injuries, and caution with unroofing of the lesions is critical to avoid additional spread.7 Knowledge of the cytologic differences of mpox compared with other viral infections is important in the early recognition, diagnosis, and treatment of these patients.

Dermatology

A woman in her 30s with AIDS presented with acute-onset painful scattered umbilicated papulopustules and ovoid ulcerated plaques with elevated, pink borders on the face, trunk, and extremities (Figure, A). The woman also had a new-onset cough but was afebrile and denied other systemic symptoms. Due to her significant immunocompromise, the clinical presentation was highly suspicious for infection. For rapid bedside differentiation of multiple infectious etiologies, a Tzanck smear was performed by scraping the base of an ulcerated lesion and inner aspect of a pseudopustule and scraping its base with a #15 blade. These contents were placed on a glass slide, fixed, and stained with Wright-Giemsa and subsequently Papanicolaou staining to further characterize the changes seen.A, Clinical image demonstrating papulopustules and ovoid ulcerated plaques with elevated, pink borders on the elbows. B, Tzanck smear using Wright-Giemsa staining of specimen demonstrating ballooning of keratinocytes and peripheralization of nuclear material (original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Herpes simplex virus

Mpox

Histoplasmosis

Molluscum contagiosum

b

female

31-40

augmented_female_frommale

https://jamanetwork.com/journals/jamadermatology/fullarticle/2811083

A man in his 30s with AIDS presented with acute-onset painful scattered umbilicated papulopustules and ovoid ulcerated plaques with elevated, pink borders on the face, trunk, and extremities (Figure, A). The patient also had a new-onset cough but was afebrile and denied other systemic symptoms. Due to his significant immunocompromise, the clinical presentation was highly suspicious for infection. For rapid bedside differentiation of multiple infectious etiologies, a Tzanck smear was performed by scraping the base of an ulcerated lesion and inner aspect of a pseudopustule and scraping its base with a #15 blade. These contents were placed on a glass slide, fixed, and stained with Wright-Giemsa and subsequently Papanicolaou staining to further characterize the changes seen.A, Clinical image demonstrating papulopustules and ovoid ulcerated plaques with elevated, pink borders on the elbows. B, Tzanck smear using Wright-Giemsa staining of specimen demonstrating ballooning of keratinocytes and peripheralization of nuclear material (original magnification ×20). What Is Your Diagnosis?

Herpes simplex virus

Histoplasmosis

Molluscum contagiosum

Mpox

D. Mpox

D

Mpox

The photographs demonstrate a Tzanck smear using Wright-Giemsa stain (Figure, B) with large ballooning keratinocytes with peripheral nuclear staining seen in a patient with subsequently polymerase chain reaction (PCR)-confirmed mpox. Mpox is a member of the pox virus family, which presents with nonspecific symptoms such as fever followed by characteristic skin changes including macules, papules, vesicles, and pustules progressing with cephalocaudal spread or in the genital and/or gluteal region in the most recent outbreak. On histopathologic findings, mpox features vary depending on the stage of the lesion.1,2 Early lesions tend to demonstrate ballooning degeneration, whereas later lesions have few viable keratinocytes.2 The viral cytopathic changes, most often seen in pseudopustular lesions, include multinucleated keratinocytes with ground glass appearance and nuclear contents pushed to the periphery, resulting in a basophilic halo.2 The lack of a true pustule with collections of neutrophils in the stratum corneum have led some to describe these lesions as pseudopustular.Tzanck smear is an inexpensive, rapid, and simple technique to perform cytologic analysis from skin. Initially described in 1947 by Arnault Tzanck for diagnosing vesiculobullous disorders, it is commonly used in diagnosing herpetic infections, which have characteristic features of acantholysis, acute inflammation, and keratinocytic ballooning and specific nuclear changes of molding, multinucleation, and chromatin margination.3 The findings of acantholysis and nuclear cytopathic changes are similarly seen in histopathologic examination of herpes simplex virus (HSV). Herpetic infections may present with clustered vesicles with a pink inflammatory rim, although more verrucous lesions have been described in immunosuppressed patients.In the Tzanck smear from a lesion of mpox in this patient (Figure, B), enlarged keratinocytes were seen with expanded cytoplasm and nuclear material pushed to the periphery, and the nuclear changes associated with HSV were all absent. The observed difference in cytologic features including the nuclear material rimming or pushed to the periphery of the cells is due to the location of viral replication; herpes viruses replicate in the nucleus, whereas mpox replicates in the cytoplasm.4 Although not part of routine practice, Papanicolaou staining was performed in this case to confirm infected cells and provide additional nuclear detail because Tzanck smears in patients with mpox were not previously reported. The findings highlighted the peripheralization of nuclear material in cells with eosinophilic staining, confirming the keratinocyte origin to the cells. A background inflammatory infiltrate was noted and can be seen in most infections.Tzanck smear can also be used to diagnose other viral and fungal infections. Molluscum contagiosum, which presents with multiple umbilicated papules, demonstrates the characteristic large (30-40 µm) ovoid homogenous basophilic staining keratinocytes called Henderson-Patterson bodies that correspond to the identically named intracytoplasmic inclusions seen on histopathologic findings.5,6 Using bedside diagnostics (including Wright Giemsa staining), blastomycosis is diagnosed with 8- to 15-µm spores with broad-based budding, similar in appearance to the organism in histologic examination.5 Histoplasmosis has small (2 to 3 µm) intracellular organisms in macrophages with artifactual clearing (pseudocapsule).5 Both of these fungal infections may manifest clinically as nonhealing ulcerations, verrucous plaques, or multiple papules or nodules and can histologically demonstrate pseudoepitheliomatous hyperplasia with characteristic organisms. The use of the Tzanck smear in diagnosis of any infection depends on the timing of the lesion and is most sensitive with vesicular or pustular lesions.6 Although we only tested 1 stage of lesions, we hypothesize this test will similarly be more sensitive for earlier lesions in patients with mpox.Tzanck smear is a useful technique that can be used to differentiate mpox from other infections at the bedside or in remote settings where PCR or additional culture techniques are not easily accessible. Infection prevention and control precautions are important to help prevent additional spread of this virus with sharp injuries, and caution with unroofing of the lesions is critical to avoid additional spread.7 Knowledge of the cytologic differences of mpox compared with other viral infections is important in the early recognition, diagnosis, and treatment of these patients.

Dermatology

A patient in their 30s with AIDS presented with acute-onset painful scattered umbilicated papulopustules and ovoid ulcerated plaques with elevated, pink borders on the face, trunk, and extremities (Figure, A). The patient also had a new-onset cough but was afebrile and denied other systemic symptoms. Due to their significant immunocompromise, the clinical presentation was highly suspicious for infection. For rapid bedside differentiation of multiple infectious etiologies, a Tzanck smear was performed by scraping the base of an ulcerated lesion and inner aspect of a pseudopustule and scraping its base with a #15 blade. These contents were placed on a glass slide, fixed, and stained with Wright-Giemsa and subsequently Papanicolaou staining to further characterize the changes seen.A, Clinical image demonstrating papulopustules and ovoid ulcerated plaques with elevated, pink borders on the elbows. B, Tzanck smear using Wright-Giemsa staining of specimen demonstrating ballooning of keratinocytes and peripheralization of nuclear material (original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Herpes simplex virus

Mpox

Histoplasmosis

Molluscum contagiosum

b

neutral

31-40

augmented_neutral_frommale

https://jamanetwork.com/journals/jama/fullarticle/2810596

An 80-year-old man with stage II bladder carcinoma (T2NXM0) and atrial fibrillation treated with apixaban presented to the emergency department with 1 week of fatigue and 2 days of dyspnea on exertion. One week prior to presentation, he received a fourth cycle of carboplatin/gemcitabine for bladder carcinoma with 6 mg of pegylated granulocyte colony-stimulating factor (G-CSF). The patient reported no anorexia, fever, melena, hematemesis, hematuria, cough, orthopnea, or peripheral edema.His vital signs were normal except for a heart rate of 103/min. His white blood cell count was 22 × 103/μL (reference, 4-11 × 103/μL), increased from 4.8 × 103/μL 8 days prior. His manual differential, which was previously normal, showed 18% bands (0%-10%), 2% metamyelocytes, 7% myelocytes, 7% promyelocytes, and 6% blasts. His hemoglobin level was 5.2 g/dL (reference, 13-17 g/dL), decreased from 7.4 g/dL, and platelets were 25 × 103/μL (reference, 150-420 × 103/μL), decreased from 268 × 103/μL 8 days prior. Ferritin was 1423 ng/mL (reference, 300-400 ng/mL). Mean corpuscular volume, prothrombin time, international normalized ratio, partial thromboplastin time, fibrinogen, haptoglobin, vitamin B12, and methylmalonic acid values were normal, and results of a direct antiglobulin test were negative. A computed tomography (CT) scan of his abdomen and pelvis was normal. He received 2 units of packed red blood cells and was admitted to the hospital. Flow cytometry identified a small population of CD34+/CD117+ cells (Figure).Left, Peripheral blood smear showing normocytic anemia with anisopoikilocytosis and leukocytosis with 6% to 8% blast forms. Right, Flow cytometry of peripheral blood demonstrating a small population of white blood cells that stained positive for CD34 and CD117, which are markers of immature myeloblasts.Esophagogastroduodenoscopy revealed 2 nonbleeding angioectasias in the stomach that were treated with argon plasma coagulation. Three days after admission, his white blood cell count was 27.7 × 103/μL with 4% peripheral blasts, hemoglobin was 7.3 g/dL, and platelet count had increased to 92 × 103/μL without a platelet transfusion.Repeat complete blood cell count with differential in 1 to 2 weeks What Would You Do Next?

Perform a bone marrow biopsy

Prescribe all-trans retinoic acid

Repeat complete blood cell count with differential in 1 to 2 weeks

Start cytoreductive therapy with hydroxyurea

Granulocyte colony-stimulating factor (G-CSF)–induced increase in peripheral blasts

C

Repeat complete blood cell count with differential in 1 to 2 weeks

The key to the correct diagnosis is recognizing that leukocytosis with immature granulocytes and mildly elevated blasts in the peripheral blood can occur after G-CSF administration. Bone marrow biopsy (choice A) is incorrect because his platelet count increased spontaneously 3 days after presentation, making malignant infiltration of his bone marrow unlikely, and recent G-CSF administration can alter bone marrow biopsy results. All-trans retinoic acid and cytoreductive therapy (options B and D) should not be prescribed because the patient did not have biopsy-proven acute promyelocytic leukemia or acute leukemia.Myeloblasts are immature leukocytes that arise from progenitor stem cells in the bone marrow, and their presence in peripheral blood suggests a perturbation of normal hematopoietic differentiation. Myeloblasts are characterized by the presence of CD34 and CD1171 antigens, identified with flow cytometry. A peripheral blood myeloblast count of greater than 20% is diagnostic of acute myeloid leukemia (AML), although AML can occur with a lower myeloblast count.2 Increased peripheral blood myeloblasts with leukopenia may be due to AML, myelodysplastic syndrome (MDS), chemotherapy, or occasionally severe infection. Causes of elevated peripheral blood myeloblasts with leukocytosis include AML, myelodysplastic syndrome, myeloproliferative neoplasms, severe infection, bone marrow damage or infiltration by fibrosis, malignancy or infection,3,4 and administration of G-CSF.G-CSF, which is produced by macrophages, T cells, endothelial cells, and fibroblasts,5 causes proliferation and differentiation of hematopoietic stem cells and progenitor cells, generating polymorphonuclear neutrophils via the precursor stages of myeloblast, promyelocyte, myelocyte, metamyelocyte, and bands. G-CSF therapy stimulates neutrophil production in the bone marrow, causing a rapid increase in peripheral blood neutrophils (emergency granulopoiesis) during severe infections. G-CSF also acts to maintain a neutrophil reserve in the bone marrow and regulates the slow release of neutrophils into the peripheral circulation.3Recombinant human G-CSF (filgrastim) received US Food and Drug Administration (FDA) approval in 1991 for prevention of chemotherapy-induced neutropenia.3,5 In 2002, the FDA approved pegfilgrastim, which is administered once per chemotherapy cycle, with at least 12 days between doses.6,7 G-CSF use is typically recommended during all chemotherapy cycles in which there is greater than 20% risk of febrile neutropenia.7 G-CSF can also be given to prevent infection in patients who experienced neutropenic complications during a prior round of chemotherapy.Patients treated with G-CSF may have peripheral blasts as high as 40% of circulating leukocytes.8 Although the mechanism of action is uncertain, induction of peripheral blasts by G-CSF may be related to differential expression of isoforms or gene variants in the G-CSF receptor. G-CSF–induced transient increase in peripheral blasts, which is most commonly reported in patients with MDS, AML, and other hematologic malignancies, is treated by withholding G-CSF therapy.3,8-10 Peripheral blasts typically resolve 1 to 2 weeks after peak blast count,8,9 at which point G-CSF therapy can be reinitiated with close monitoring of blood counts.After a 3-day hospitalization, the patient had a white blood cell count of 22.7 × 103/μL with 9% bands, 2% metamyelocytes, 2% myelocytes, 2% promyelocytes, and 4% blasts; hemoglobin was 7.3 g/dL, and platelets were 92 × 103/μL. Ten days after hospital discharge, his white blood cell count was 7.4 × 103/μL with a normal differential and no blasts; hemoglobin was 8.9 g/dL, and platelets were 384 × 103/μL. Two months later, he underwent cystectomy and received treatment with nivolumab for 5 months. However, his cancer progressed, and the patient died 5 months after his initial presentation.

General

An 80-year-old man with stage II bladder carcinoma (T2NXM0) and atrial fibrillation treated with apixaban presented to the emergency department with 1 week of fatigue and 2 days of dyspnea on exertion. One week prior to presentation, he received a fourth cycle of carboplatin/gemcitabine for bladder carcinoma with 6 mg of pegylated granulocyte colony-stimulating factor (G-CSF). The patient reported no anorexia, fever, melena, hematemesis, hematuria, cough, orthopnea, or peripheral edema.His vital signs were normal except for a heart rate of 103/min. His white blood cell count was 22 × 103/μL (reference, 4-11 × 103/μL), increased from 4.8 × 103/μL 8 days prior. His manual differential, which was previously normal, showed 18% bands (0%-10%), 2% metamyelocytes, 7% myelocytes, 7% promyelocytes, and 6% blasts. His hemoglobin level was 5.2 g/dL (reference, 13-17 g/dL), decreased from 7.4 g/dL, and platelets were 25 × 103/μL (reference, 150-420 × 103/μL), decreased from 268 × 103/μL 8 days prior. Ferritin was 1423 ng/mL (reference, 300-400 ng/mL). Mean corpuscular volume, prothrombin time, international normalized ratio, partial thromboplastin time, fibrinogen, haptoglobin, vitamin B12, and methylmalonic acid values were normal, and results of a direct antiglobulin test were negative. A computed tomography (CT) scan of his abdomen and pelvis was normal. He received 2 units of packed red blood cells and was admitted to the hospital. Flow cytometry identified a small population of CD34+/CD117+ cells (Figure).Left, Peripheral blood smear showing normocytic anemia with anisopoikilocytosis and leukocytosis with 6% to 8% blast forms. Right, Flow cytometry of peripheral blood demonstrating a small population of white blood cells that stained positive for CD34 and CD117, which are markers of immature myeloblasts.Esophagogastroduodenoscopy revealed 2 nonbleeding angioectasias in the stomach that were treated with argon plasma coagulation. Three days after admission, his white blood cell count was 27.7 × 103/μL with 4% peripheral blasts, hemoglobin was 7.3 g/dL, and platelet count had increased to 92 × 103/μL without a platelet transfusion.Repeat complete blood cell count with differential in 1 to 2 weeks

what would you do next?

What would you do next?

Start cytoreductive therapy with hydroxyurea

Prescribe all-trans retinoic acid

Repeat complete blood cell count with differential in 1 to 2 weeks

Perform a bone marrow biopsy

c

male

71-80

White

original

https://jamanetwork.com/journals/jama/fullarticle/2810596

An 80-year-old man with stage II bladder carcinoma (T2NXM0) and atrial fibrillation treated with apixaban presented to the emergency department with 1 week of fatigue and 2 days of dyspnea on exertion. One week prior to presentation, he received a fourth cycle of carboplatin/gemcitabine for bladder carcinoma with 6 mg of pegylated granulocyte colony-stimulating factor (G-CSF). The patient reported no anorexia, fever, melena, hematemesis, hematuria, cough, orthopnea, or peripheral edema.His vital signs were normal except for a heart rate of 103/min. His white blood cell count was 22 × 103/μL (reference, 4-11 × 103/μL), increased from 4.8 × 103/μL 8 days prior. His manual differential, which was previously normal, showed 18% bands (0%-10%), 2% metamyelocytes, 7% myelocytes, 7% promyelocytes, and 6% blasts. His hemoglobin level was 5.2 g/dL (reference, 13-17 g/dL), decreased from 7.4 g/dL, and platelets were 25 × 103/μL (reference, 150-420 × 103/μL), decreased from 268 × 103/μL 8 days prior. Ferritin was 1423 ng/mL (reference, 300-400 ng/mL). Mean corpuscular volume, prothrombin time, international normalized ratio, partial thromboplastin time, fibrinogen, haptoglobin, vitamin B12, and methylmalonic acid values were normal, and results of a direct antiglobulin test were negative. A computed tomography (CT) scan of his abdomen and pelvis was normal. He received 2 units of packed red blood cells and was admitted to the hospital. Flow cytometry identified a small population of CD34+/CD117+ cells (Figure).Left, Peripheral blood smear showing normocytic anemia with anisopoikilocytosis and leukocytosis with 6% to 8% blast forms. Right, Flow cytometry of peripheral blood demonstrating a small population of white blood cells that stained positive for CD34 and CD117, which are markers of immature myeloblasts.Esophagogastroduodenoscopy revealed 2 nonbleeding angioectasias in the stomach that were treated with argon plasma coagulation. Three days after admission, his white blood cell count was 27.7 × 103/μL with 4% peripheral blasts, hemoglobin was 7.3 g/dL, and platelet count had increased to 92 × 103/μL without a platelet transfusion.Repeat complete blood cell count with differential in 1 to 2 weeks What Would You Do Next?

Perform a bone marrow biopsy

Prescribe all-trans retinoic acid

Repeat complete blood cell count with differential in 1 to 2 weeks

Start cytoreductive therapy with hydroxyurea

Granulocyte colony-stimulating factor (G-CSF)–induced increase in peripheral blasts

C

Repeat complete blood cell count with differential in 1 to 2 weeks

The key to the correct diagnosis is recognizing that leukocytosis with immature granulocytes and mildly elevated blasts in the peripheral blood can occur after G-CSF administration. Bone marrow biopsy (choice A) is incorrect because his platelet count increased spontaneously 3 days after presentation, making malignant infiltration of his bone marrow unlikely, and recent G-CSF administration can alter bone marrow biopsy results. All-trans retinoic acid and cytoreductive therapy (options B and D) should not be prescribed because the patient did not have biopsy-proven acute promyelocytic leukemia or acute leukemia.Myeloblasts are immature leukocytes that arise from progenitor stem cells in the bone marrow, and their presence in peripheral blood suggests a perturbation of normal hematopoietic differentiation. Myeloblasts are characterized by the presence of CD34 and CD1171 antigens, identified with flow cytometry. A peripheral blood myeloblast count of greater than 20% is diagnostic of acute myeloid leukemia (AML), although AML can occur with a lower myeloblast count.2 Increased peripheral blood myeloblasts with leukopenia may be due to AML, myelodysplastic syndrome (MDS), chemotherapy, or occasionally severe infection. Causes of elevated peripheral blood myeloblasts with leukocytosis include AML, myelodysplastic syndrome, myeloproliferative neoplasms, severe infection, bone marrow damage or infiltration by fibrosis, malignancy or infection,3,4 and administration of G-CSF.G-CSF, which is produced by macrophages, T cells, endothelial cells, and fibroblasts,5 causes proliferation and differentiation of hematopoietic stem cells and progenitor cells, generating polymorphonuclear neutrophils via the precursor stages of myeloblast, promyelocyte, myelocyte, metamyelocyte, and bands. G-CSF therapy stimulates neutrophil production in the bone marrow, causing a rapid increase in peripheral blood neutrophils (emergency granulopoiesis) during severe infections. G-CSF also acts to maintain a neutrophil reserve in the bone marrow and regulates the slow release of neutrophils into the peripheral circulation.3Recombinant human G-CSF (filgrastim) received US Food and Drug Administration (FDA) approval in 1991 for prevention of chemotherapy-induced neutropenia.3,5 In 2002, the FDA approved pegfilgrastim, which is administered once per chemotherapy cycle, with at least 12 days between doses.6,7 G-CSF use is typically recommended during all chemotherapy cycles in which there is greater than 20% risk of febrile neutropenia.7 G-CSF can also be given to prevent infection in patients who experienced neutropenic complications during a prior round of chemotherapy.Patients treated with G-CSF may have peripheral blasts as high as 40% of circulating leukocytes.8 Although the mechanism of action is uncertain, induction of peripheral blasts by G-CSF may be related to differential expression of isoforms or gene variants in the G-CSF receptor. G-CSF–induced transient increase in peripheral blasts, which is most commonly reported in patients with MDS, AML, and other hematologic malignancies, is treated by withholding G-CSF therapy.3,8-10 Peripheral blasts typically resolve 1 to 2 weeks after peak blast count,8,9 at which point G-CSF therapy can be reinitiated with close monitoring of blood counts.After a 3-day hospitalization, the patient had a white blood cell count of 22.7 × 103/μL with 9% bands, 2% metamyelocytes, 2% myelocytes, 2% promyelocytes, and 4% blasts; hemoglobin was 7.3 g/dL, and platelets were 92 × 103/μL. Ten days after hospital discharge, his white blood cell count was 7.4 × 103/μL with a normal differential and no blasts; hemoglobin was 8.9 g/dL, and platelets were 384 × 103/μL. Two months later, he underwent cystectomy and received treatment with nivolumab for 5 months. However, his cancer progressed, and the patient died 5 months after his initial presentation.

General

An 80-year-old woman with stage II bladder carcinoma (T2NXM0) and atrial fibrillation treated with apixaban presented to the emergency department with 1 week of fatigue and 2 days of dyspnea on exertion. One week prior to presentation, she received a fourth cycle of carboplatin/gemcitabine for bladder carcinoma with 6 mg of pegylated granulocyte colony-stimulating factor (G-CSF). The woman reported no anorexia, fever, melena, hematemesis, hematuria, cough, orthopnea, or peripheral edema.Her vital signs were normal except for a heart rate of 103/min. Her white blood cell count was 22 × 103/μL (reference, 4-11 × 103/μL), increased from 4.8 × 103/μL 8 days prior. Her manual differential, which was previously normal, showed 18% bands (0%-10%), 2% metamyelocytes, 7% myelocytes, 7% promyelocytes, and 6% blasts. Her hemoglobin level was 5.2 g/dL (reference, 13-17 g/dL), decreased from 7.4 g/dL, and platelets were 25 × 103/μL (reference, 150-420 × 103/μL), decreased from 268 × 103/μL 8 days prior. Ferritin was 1423 ng/mL (reference, 300-400 ng/mL). Mean corpuscular volume, prothrombin time, international normalized ratio, partial thromboplastin time, fibrinogen, haptoglobin, vitamin B12, and methylmalonic acid values were normal, and results of a direct antiglobulin test were negative. A computed tomography (CT) scan of her abdomen and pelvis was normal. She received 2 units of packed red blood cells and was admitted to the hospital. Flow cytometry identified a small population of CD34+/CD117+ cells (Figure).Left, Peripheral blood smear showing normocytic anemia with anisopoikilocytosis and leukocytosis with 6% to 8% blast forms. Right, Flow cytometry of peripheral blood demonstrating a small population of white blood cells that stained positive for CD34 and CD117, which are markers of immature myeloblasts.Esophagogastroduodenoscopy revealed 2 nonbleeding angioectasias in the stomach that were treated with argon plasma coagulation. Three days after admission, her white blood cell count was 27.7 × 103/μL with 4% peripheral blasts, hemoglobin was 7.3 g/dL, and platelet count had increased to 92 × 103/μL without a platelet transfusion.Repeat complete blood cell count with differential in 1 to 2 weeks

what would you do next?

What would you do next?

Start cytoreductive therapy with hydroxyurea

Prescribe all-trans retinoic acid

Repeat complete blood cell count with differential in 1 to 2 weeks

Perform a bone marrow biopsy

c

female

71-80

White

augmented_female_frommale

https://jamanetwork.com/journals/jama/fullarticle/2810596

An 80-year-old man with stage II bladder carcinoma (T2NXM0) and atrial fibrillation treated with apixaban presented to the emergency department with 1 week of fatigue and 2 days of dyspnea on exertion. One week prior to presentation, he received a fourth cycle of carboplatin/gemcitabine for bladder carcinoma with 6 mg of pegylated granulocyte colony-stimulating factor (G-CSF). The patient reported no anorexia, fever, melena, hematemesis, hematuria, cough, orthopnea, or peripheral edema.His vital signs were normal except for a heart rate of 103/min. His white blood cell count was 22 × 103/μL (reference, 4-11 × 103/μL), increased from 4.8 × 103/μL 8 days prior. His manual differential, which was previously normal, showed 18% bands (0%-10%), 2% metamyelocytes, 7% myelocytes, 7% promyelocytes, and 6% blasts. His hemoglobin level was 5.2 g/dL (reference, 13-17 g/dL), decreased from 7.4 g/dL, and platelets were 25 × 103/μL (reference, 150-420 × 103/μL), decreased from 268 × 103/μL 8 days prior. Ferritin was 1423 ng/mL (reference, 300-400 ng/mL). Mean corpuscular volume, prothrombin time, international normalized ratio, partial thromboplastin time, fibrinogen, haptoglobin, vitamin B12, and methylmalonic acid values were normal, and results of a direct antiglobulin test were negative. A computed tomography (CT) scan of his abdomen and pelvis was normal. He received 2 units of packed red blood cells and was admitted to the hospital. Flow cytometry identified a small population of CD34+/CD117+ cells (Figure).Left, Peripheral blood smear showing normocytic anemia with anisopoikilocytosis and leukocytosis with 6% to 8% blast forms. Right, Flow cytometry of peripheral blood demonstrating a small population of white blood cells that stained positive for CD34 and CD117, which are markers of immature myeloblasts.Esophagogastroduodenoscopy revealed 2 nonbleeding angioectasias in the stomach that were treated with argon plasma coagulation. Three days after admission, his white blood cell count was 27.7 × 103/μL with 4% peripheral blasts, hemoglobin was 7.3 g/dL, and platelet count had increased to 92 × 103/μL without a platelet transfusion.Repeat complete blood cell count with differential in 1 to 2 weeks What Would You Do Next?

Perform a bone marrow biopsy

Prescribe all-trans retinoic acid

Repeat complete blood cell count with differential in 1 to 2 weeks

Start cytoreductive therapy with hydroxyurea

Granulocyte colony-stimulating factor (G-CSF)–induced increase in peripheral blasts

C

Repeat complete blood cell count with differential in 1 to 2 weeks

The key to the correct diagnosis is recognizing that leukocytosis with immature granulocytes and mildly elevated blasts in the peripheral blood can occur after G-CSF administration. Bone marrow biopsy (choice A) is incorrect because his platelet count increased spontaneously 3 days after presentation, making malignant infiltration of his bone marrow unlikely, and recent G-CSF administration can alter bone marrow biopsy results. All-trans retinoic acid and cytoreductive therapy (options B and D) should not be prescribed because the patient did not have biopsy-proven acute promyelocytic leukemia or acute leukemia.Myeloblasts are immature leukocytes that arise from progenitor stem cells in the bone marrow, and their presence in peripheral blood suggests a perturbation of normal hematopoietic differentiation. Myeloblasts are characterized by the presence of CD34 and CD1171 antigens, identified with flow cytometry. A peripheral blood myeloblast count of greater than 20% is diagnostic of acute myeloid leukemia (AML), although AML can occur with a lower myeloblast count.2 Increased peripheral blood myeloblasts with leukopenia may be due to AML, myelodysplastic syndrome (MDS), chemotherapy, or occasionally severe infection. Causes of elevated peripheral blood myeloblasts with leukocytosis include AML, myelodysplastic syndrome, myeloproliferative neoplasms, severe infection, bone marrow damage or infiltration by fibrosis, malignancy or infection,3,4 and administration of G-CSF.G-CSF, which is produced by macrophages, T cells, endothelial cells, and fibroblasts,5 causes proliferation and differentiation of hematopoietic stem cells and progenitor cells, generating polymorphonuclear neutrophils via the precursor stages of myeloblast, promyelocyte, myelocyte, metamyelocyte, and bands. G-CSF therapy stimulates neutrophil production in the bone marrow, causing a rapid increase in peripheral blood neutrophils (emergency granulopoiesis) during severe infections. G-CSF also acts to maintain a neutrophil reserve in the bone marrow and regulates the slow release of neutrophils into the peripheral circulation.3Recombinant human G-CSF (filgrastim) received US Food and Drug Administration (FDA) approval in 1991 for prevention of chemotherapy-induced neutropenia.3,5 In 2002, the FDA approved pegfilgrastim, which is administered once per chemotherapy cycle, with at least 12 days between doses.6,7 G-CSF use is typically recommended during all chemotherapy cycles in which there is greater than 20% risk of febrile neutropenia.7 G-CSF can also be given to prevent infection in patients who experienced neutropenic complications during a prior round of chemotherapy.Patients treated with G-CSF may have peripheral blasts as high as 40% of circulating leukocytes.8 Although the mechanism of action is uncertain, induction of peripheral blasts by G-CSF may be related to differential expression of isoforms or gene variants in the G-CSF receptor. G-CSF–induced transient increase in peripheral blasts, which is most commonly reported in patients with MDS, AML, and other hematologic malignancies, is treated by withholding G-CSF therapy.3,8-10 Peripheral blasts typically resolve 1 to 2 weeks after peak blast count,8,9 at which point G-CSF therapy can be reinitiated with close monitoring of blood counts.After a 3-day hospitalization, the patient had a white blood cell count of 22.7 × 103/μL with 9% bands, 2% metamyelocytes, 2% myelocytes, 2% promyelocytes, and 4% blasts; hemoglobin was 7.3 g/dL, and platelets were 92 × 103/μL. Ten days after hospital discharge, his white blood cell count was 7.4 × 103/μL with a normal differential and no blasts; hemoglobin was 8.9 g/dL, and platelets were 384 × 103/μL. Two months later, he underwent cystectomy and received treatment with nivolumab for 5 months. However, his cancer progressed, and the patient died 5 months after his initial presentation.

General

An 80-year-old patient with stage II bladder carcinoma (T2NXM0) and atrial fibrillation treated with apixaban presented to the emergency department with 1 week of fatigue and 2 days of dyspnea on exertion. One week prior to presentation, they received a fourth cycle of carboplatin/gemcitabine for bladder carcinoma with 6 mg of pegylated granulocyte colony-stimulating factor (G-CSF). The patient reported no anorexia, fever, melena, hematemesis, hematuria, cough, orthopnea, or peripheral edema.Their vital signs were normal except for a heart rate of 103/min. Their white blood cell count was 22 × 103/μL (reference, 4-11 × 103/μL), increased from 4.8 × 103/μL 8 days prior. Their manual differential, which was previously normal, showed 18% bands (0%-10%), 2% metamyelocytes, 7% myelocytes, 7% promyelocytes, and 6% blasts. Their hemoglobin level was 5.2 g/dL (reference, 13-17 g/dL), decreased from 7.4 g/dL, and platelets were 25 × 103/μL (reference, 150-420 × 103/μL), decreased from 268 × 103/μL 8 days prior. Ferritin was 1423 ng/mL (reference, 300-400 ng/mL). Mean corpuscular volume, prothrombin time, international normalized ratio, partial thromboplastin time, fibrinogen, haptoglobin, vitamin B12, and methylmalonic acid values were normal, and results of a direct antiglobulin test were negative. A computed tomography (CT) scan of their abdomen and pelvis was normal. They received 2 units of packed red blood cells and was admitted to the hospital. Flow cytometry identified a small population of CD34+/CD117+ cells (Figure).Left, Peripheral blood smear showing normocytic anemia with anisopoikilocytosis and leukocytosis with 6% to 8% blast forms. Right, Flow cytometry of peripheral blood demonstrating a small population of white blood cells that stained positive for CD34 and CD117, which are markers of immature myeloblasts.Esophagogastroduodenoscopy revealed 2 nonbleeding angioectasias in the stomach that were treated with argon plasma coagulation. Three days after admission, their white blood cell count was 27.7 × 103/μL with 4% peripheral blasts, hemoglobin was 7.3 g/dL, and platelet count had increased to 92 × 103/μL without a platelet transfusion.Repeat complete blood cell count with differential in 1 to 2 weeks

what would you do next?

What would you do next?

Start cytoreductive therapy with hydroxyurea

Prescribe all-trans retinoic acid

Repeat complete blood cell count with differential in 1 to 2 weeks

Perform a bone marrow biopsy

c

neutral

71-80

White

augmented_neutral_frommale

https://jamanetwork.com/journals/jamaneurology/fullarticle/2810537

A 68-year-old man presented with progressive right-sided facial numbness and weakness, vision changes, and headaches. His symptoms began 5 years earlier with right temple numbness, which expanded to include the entire right face and mouth. He then developed progressive right facial weakness with a droop, slurred speech, and eyelid ptosis. Finally, binocular vertical and horizontal diplopia and periorbital headaches began. Trials of gabapentin and steroids provided no relief. His history was significant for a left cheek melanoma completely excised years prior, numerous cutaneous squamous and basal cell carcinomas of the bilateral head and neck removed without issue, type 2 diabetes, and hyperlipidemia. His medications included metformin and simvastatin; he had no history of smoking or drinking.On examination, he had right-sided ptosis and severe right facial weakness in a lower motor neuron pattern with temporal wasting. The right pupil was fixed and dilated. There was no afferent pupillary defect. The left pupil was appropriately sized and reactive. His right-sided vision was impaired (20/250) with blurriness. Vertical and horizontal binocular diplopia was present. Right extraocular movements were significantly limited in all directions and painful, and right-sided facial sensation was diminished to pinprick in all cranial nerve (CN) V distributions. His speech was slightly slurred. Left-sided extraocular movements were intact. His left facial sensation was intact to pinprick, and his strength was without deficit. There were no other neurological abnormalities.Initial magnetic resonance images (MRIs) were unremarkable. A biopsy of CN VII was nondiagnostic. Hemoglobin A1c was 6.8%. Tests for infection and autoimmune disease had negative results. Cerebrospinal fluid (CSF) studies showed mildly elevated protein values. Figure 1 shows the MRI at presentation.T1 turbo spin-echo fat-saturated magnetic resonance images of the brain through the skull base at presentation. What Is Your Diagnosis?

Primary leptomeningeal lymphoma

Tolosa-Hunt syndrome

Perineural spread of cutaneous malignancy

Sphenoid wing meningioma

C. Perineural spread of cutaneous malignancy

C

Perineural spread of cutaneous malignancy

The MRI of the brain and orbits revealed asymmetric enhancement of the right CNs V and VII, with denervation atrophy of the masticator space (Figure 2). Biopsy of the infraorbital nerve revealed squamous cell carcinoma, thought to have originated from a cutaneous source given his history. Immunotherapy was initiated with cemiplimab. MRI findings have remained stable over the past 2 years with no progression of disease or worsening symptoms.Same magnetic resonance image as in Figure 1B with an arrowhead denoting asymmetric enhancement of the right maxillary nerve in the foramen rotundum.The onset of multiple cranial neuropathies presents a diagnostic dilemma. Oncological diagnosis is often difficult in the absence of an obvious lesion and normal or equivocal imaging.1 This can lead to diagnostic delays and worse outcomes. This patient was seen by 20 different physicians over 5 years, including general, autonomic, and neuromuscular neurologists and neuro-ophthalmologists, before a diagnosis of malignancy was made. It can take time for perineural invasion (PNI) to become radiographically apparent, and a high index of suspicion for underlying malignancy must be maintained even with initially negative imaging.Primary leptomeningeal lymphoma (A) is a rare manifestation of primary central nervous system lymphoma that can present with multiple cranial neuropathies.2 CSF results are usually abnormal and progression of symptoms more rapid.2 Tolosa-Hunt syndrome (B) can present with painful ophthalmoplegia and multiple cranial neuropathies; however, steroids are typically effective.3 When located along the sphenoid wing, meningiomas (D) can cause multiple progressive cranial neuropathies.4 Typically visible on MRI as extra-axial homogenously enhancing masses,4 no such lesion was observed here. In this patient, the symptomatology, history, and radiographic findings are best explained by PNI of cutaneous squamous cell carcinoma (cSCC), which a biopsy confirmed.One of the most common cancers in the world, cSCC occurs frequently in the head and neck secondary to sun exposure.5 PNI refers to the process of tumor spread into nerves and the space surrounding them.6 An estimated 2% to 6% of patients with cSCC of the head and neck will have PNI.1,6 Cranial nerves V and VII are most commonly involved given their extensive anatomical distributions.1,5,6 Clinically or radiographically apparent PNI confers a poor prognosis with a reported 5-year absolute survival rate of 50%.5Treatment for cSCC of the head and neck includes surgery (if resectable) and high-dose radiotherapy and systemic therapy as appropriate. Immunotherapy with checkpoint inhibition is being used with increasing frequency and notable effectiveness.5-9 Early-phase studies demonstrated impressive response rates near 50% for advanced, unresectable, and metastatic cSCC of the head and neck, earning US Food and Drug Administration approval for 2 checkpoint inhibitors in this setting.7,8 Recently, a landmark phase 2 trial of neoadjuvant cemiplimab for stage II through IV (M0) cSCC before surgery was published, with 51% complete pathological response rates and 68% objective response rates on imaging.9 Similarly, in a recent report of 11 patients with cSCC of the head and neck with clinical PNI treated with checkpoint inhibitors, radiographic disease control was observed in 9 of 11 patients at extended follow-up.5 Many of these responses are durable and curative.The presence of both CN V and VII symptoms in a patient with a history of head and neck cSCC should raise suspicion for perineural recurrence of disease. While initial MRI may be negative, radiographic manifestation of PNI often occurs over time as the disease progresses and symptoms worsen. Expert review by a neuroradiologist can be helpful in identifying this finding earlier in the disease course. Mounting evidence suggests that immunotherapy is a promising treatment option for this population and should be considered as first-line therapy.

Neurology

A 68-year-old man presented with progressive right-sided facial numbness and weakness, vision changes, and headaches. His symptoms began 5 years earlier with right temple numbness, which expanded to include the entire right face and mouth. He then developed progressive right facial weakness with a droop, slurred speech, and eyelid ptosis. Finally, binocular vertical and horizontal diplopia and periorbital headaches began. Trials of gabapentin and steroids provided no relief. His history was significant for a left cheek melanoma completely excised years prior, numerous cutaneous squamous and basal cell carcinomas of the bilateral head and neck removed without issue, type 2 diabetes, and hyperlipidemia. His medications included metformin and simvastatin; he had no history of smoking or drinking.On examination, he had right-sided ptosis and severe right facial weakness in a lower motor neuron pattern with temporal wasting. The right pupil was fixed and dilated. There was no afferent pupillary defect. The left pupil was appropriately sized and reactive. His right-sided vision was impaired (20/250) with blurriness. Vertical and horizontal binocular diplopia was present. Right extraocular movements were significantly limited in all directions and painful, and right-sided facial sensation was diminished to pinprick in all cranial nerve (CN) V distributions. His speech was slightly slurred. Left-sided extraocular movements were intact. His left facial sensation was intact to pinprick, and his strength was without deficit. There were no other neurological abnormalities.Initial magnetic resonance images (MRIs) were unremarkable. A biopsy of CN VII was nondiagnostic. Hemoglobin A1c was 6.8%. Tests for infection and autoimmune disease had negative results. Cerebrospinal fluid (CSF) studies showed mildly elevated protein values. Figure 1 shows the MRI at presentation.T1 turbo spin-echo fat-saturated magnetic resonance images of the brain through the skull base at presentation.

what is your diagnosis?

What is your diagnosis?

Tolosa-Hunt syndrome

Perineural spread of cutaneous malignancy

Sphenoid wing meningioma

Primary leptomeningeal lymphoma

b

male

61-70

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2810537

A 68-year-old man presented with progressive right-sided facial numbness and weakness, vision changes, and headaches. His symptoms began 5 years earlier with right temple numbness, which expanded to include the entire right face and mouth. He then developed progressive right facial weakness with a droop, slurred speech, and eyelid ptosis. Finally, binocular vertical and horizontal diplopia and periorbital headaches began. Trials of gabapentin and steroids provided no relief. His history was significant for a left cheek melanoma completely excised years prior, numerous cutaneous squamous and basal cell carcinomas of the bilateral head and neck removed without issue, type 2 diabetes, and hyperlipidemia. His medications included metformin and simvastatin; he had no history of smoking or drinking.On examination, he had right-sided ptosis and severe right facial weakness in a lower motor neuron pattern with temporal wasting. The right pupil was fixed and dilated. There was no afferent pupillary defect. The left pupil was appropriately sized and reactive. His right-sided vision was impaired (20/250) with blurriness. Vertical and horizontal binocular diplopia was present. Right extraocular movements were significantly limited in all directions and painful, and right-sided facial sensation was diminished to pinprick in all cranial nerve (CN) V distributions. His speech was slightly slurred. Left-sided extraocular movements were intact. His left facial sensation was intact to pinprick, and his strength was without deficit. There were no other neurological abnormalities.Initial magnetic resonance images (MRIs) were unremarkable. A biopsy of CN VII was nondiagnostic. Hemoglobin A1c was 6.8%. Tests for infection and autoimmune disease had negative results. Cerebrospinal fluid (CSF) studies showed mildly elevated protein values. Figure 1 shows the MRI at presentation.T1 turbo spin-echo fat-saturated magnetic resonance images of the brain through the skull base at presentation. What Is Your Diagnosis?

Primary leptomeningeal lymphoma

Tolosa-Hunt syndrome

Perineural spread of cutaneous malignancy

Sphenoid wing meningioma

C. Perineural spread of cutaneous malignancy

C

Perineural spread of cutaneous malignancy

The MRI of the brain and orbits revealed asymmetric enhancement of the right CNs V and VII, with denervation atrophy of the masticator space (Figure 2). Biopsy of the infraorbital nerve revealed squamous cell carcinoma, thought to have originated from a cutaneous source given his history. Immunotherapy was initiated with cemiplimab. MRI findings have remained stable over the past 2 years with no progression of disease or worsening symptoms.Same magnetic resonance image as in Figure 1B with an arrowhead denoting asymmetric enhancement of the right maxillary nerve in the foramen rotundum.The onset of multiple cranial neuropathies presents a diagnostic dilemma. Oncological diagnosis is often difficult in the absence of an obvious lesion and normal or equivocal imaging.1 This can lead to diagnostic delays and worse outcomes. This patient was seen by 20 different physicians over 5 years, including general, autonomic, and neuromuscular neurologists and neuro-ophthalmologists, before a diagnosis of malignancy was made. It can take time for perineural invasion (PNI) to become radiographically apparent, and a high index of suspicion for underlying malignancy must be maintained even with initially negative imaging.Primary leptomeningeal lymphoma (A) is a rare manifestation of primary central nervous system lymphoma that can present with multiple cranial neuropathies.2 CSF results are usually abnormal and progression of symptoms more rapid.2 Tolosa-Hunt syndrome (B) can present with painful ophthalmoplegia and multiple cranial neuropathies; however, steroids are typically effective.3 When located along the sphenoid wing, meningiomas (D) can cause multiple progressive cranial neuropathies.4 Typically visible on MRI as extra-axial homogenously enhancing masses,4 no such lesion was observed here. In this patient, the symptomatology, history, and radiographic findings are best explained by PNI of cutaneous squamous cell carcinoma (cSCC), which a biopsy confirmed.One of the most common cancers in the world, cSCC occurs frequently in the head and neck secondary to sun exposure.5 PNI refers to the process of tumor spread into nerves and the space surrounding them.6 An estimated 2% to 6% of patients with cSCC of the head and neck will have PNI.1,6 Cranial nerves V and VII are most commonly involved given their extensive anatomical distributions.1,5,6 Clinically or radiographically apparent PNI confers a poor prognosis with a reported 5-year absolute survival rate of 50%.5Treatment for cSCC of the head and neck includes surgery (if resectable) and high-dose radiotherapy and systemic therapy as appropriate. Immunotherapy with checkpoint inhibition is being used with increasing frequency and notable effectiveness.5-9 Early-phase studies demonstrated impressive response rates near 50% for advanced, unresectable, and metastatic cSCC of the head and neck, earning US Food and Drug Administration approval for 2 checkpoint inhibitors in this setting.7,8 Recently, a landmark phase 2 trial of neoadjuvant cemiplimab for stage II through IV (M0) cSCC before surgery was published, with 51% complete pathological response rates and 68% objective response rates on imaging.9 Similarly, in a recent report of 11 patients with cSCC of the head and neck with clinical PNI treated with checkpoint inhibitors, radiographic disease control was observed in 9 of 11 patients at extended follow-up.5 Many of these responses are durable and curative.The presence of both CN V and VII symptoms in a patient with a history of head and neck cSCC should raise suspicion for perineural recurrence of disease. While initial MRI may be negative, radiographic manifestation of PNI often occurs over time as the disease progresses and symptoms worsen. Expert review by a neuroradiologist can be helpful in identifying this finding earlier in the disease course. Mounting evidence suggests that immunotherapy is a promising treatment option for this population and should be considered as first-line therapy.

Neurology

A 68-year-old woman presented with progressive right-sided facial numbness and weakness, vision changes, and headaches. Her symptoms began 5 years earlier with right temple numbness, which expanded to include the entire right face and mouth. She then developed progressive right facial weakness with a droop, slurred speech, and eyelid ptosis. Finally, binocular vertical and horizontal diplopia and periorbital headaches began. Trials of gabapentin and steroids provided no relief. Her history was significant for a left cheek melanoma completely excised years prior, numerous cutaneous squamous and basal cell carcinomas of the bilateral head and neck removed without issue, type 2 diabetes, and hyperlipidemia. Her medications included metformin and simvastatin; she had no history of smoking or drinking.On examination, she had right-sided ptosis and severe right facial weakness in a lower motor neuron pattern with temporal wasting. The right pupil was fixed and dilated. There was no afferent pupillary defect. The left pupil was appropriately sized and reactive. Her right-sided vision was impaired (20/250) with blurriness. Vertical and horizontal binocular diplopia was present. Right extraocular movements were significantly limited in all directions and painful, and right-sided facial sensation was diminished to pinprick in all cranial nerve (CN) V distributions. Her speech was slightly slurred. Left-sided extraocular movements were intact. Her left facial sensation was intact to pinprick, and her strength was without deficit. There were no other neurological abnormalities.Initial magnetic resonance images (MRIs) were unremarkable. A biopsy of CN VII was nondiagnostic. Hemoglobin A1c was 6.8%. Tests for infection and autoimmune disease had negative results. Cerebrospinal fluid (CSF) studies showed mildly elevated protein values. Figure 1 shows the MRI at presentation.T1 turbo spin-echo fat-saturated magnetic resonance images of the brain through the skull base at presentation.

what is your diagnosis?

What is your diagnosis?

Tolosa-Hunt syndrome

Perineural spread of cutaneous malignancy

Sphenoid wing meningioma

Primary leptomeningeal lymphoma

b

female

61-70

augmented_female_frommale

https://jamanetwork.com/journals/jamaneurology/fullarticle/2810537

A 68-year-old man presented with progressive right-sided facial numbness and weakness, vision changes, and headaches. His symptoms began 5 years earlier with right temple numbness, which expanded to include the entire right face and mouth. He then developed progressive right facial weakness with a droop, slurred speech, and eyelid ptosis. Finally, binocular vertical and horizontal diplopia and periorbital headaches began. Trials of gabapentin and steroids provided no relief. His history was significant for a left cheek melanoma completely excised years prior, numerous cutaneous squamous and basal cell carcinomas of the bilateral head and neck removed without issue, type 2 diabetes, and hyperlipidemia. His medications included metformin and simvastatin; he had no history of smoking or drinking.On examination, he had right-sided ptosis and severe right facial weakness in a lower motor neuron pattern with temporal wasting. The right pupil was fixed and dilated. There was no afferent pupillary defect. The left pupil was appropriately sized and reactive. His right-sided vision was impaired (20/250) with blurriness. Vertical and horizontal binocular diplopia was present. Right extraocular movements were significantly limited in all directions and painful, and right-sided facial sensation was diminished to pinprick in all cranial nerve (CN) V distributions. His speech was slightly slurred. Left-sided extraocular movements were intact. His left facial sensation was intact to pinprick, and his strength was without deficit. There were no other neurological abnormalities.Initial magnetic resonance images (MRIs) were unremarkable. A biopsy of CN VII was nondiagnostic. Hemoglobin A1c was 6.8%. Tests for infection and autoimmune disease had negative results. Cerebrospinal fluid (CSF) studies showed mildly elevated protein values. Figure 1 shows the MRI at presentation.T1 turbo spin-echo fat-saturated magnetic resonance images of the brain through the skull base at presentation. What Is Your Diagnosis?

Primary leptomeningeal lymphoma

Tolosa-Hunt syndrome

Perineural spread of cutaneous malignancy

Sphenoid wing meningioma

C. Perineural spread of cutaneous malignancy

C

Perineural spread of cutaneous malignancy

The MRI of the brain and orbits revealed asymmetric enhancement of the right CNs V and VII, with denervation atrophy of the masticator space (Figure 2). Biopsy of the infraorbital nerve revealed squamous cell carcinoma, thought to have originated from a cutaneous source given his history. Immunotherapy was initiated with cemiplimab. MRI findings have remained stable over the past 2 years with no progression of disease or worsening symptoms.Same magnetic resonance image as in Figure 1B with an arrowhead denoting asymmetric enhancement of the right maxillary nerve in the foramen rotundum.The onset of multiple cranial neuropathies presents a diagnostic dilemma. Oncological diagnosis is often difficult in the absence of an obvious lesion and normal or equivocal imaging.1 This can lead to diagnostic delays and worse outcomes. This patient was seen by 20 different physicians over 5 years, including general, autonomic, and neuromuscular neurologists and neuro-ophthalmologists, before a diagnosis of malignancy was made. It can take time for perineural invasion (PNI) to become radiographically apparent, and a high index of suspicion for underlying malignancy must be maintained even with initially negative imaging.Primary leptomeningeal lymphoma (A) is a rare manifestation of primary central nervous system lymphoma that can present with multiple cranial neuropathies.2 CSF results are usually abnormal and progression of symptoms more rapid.2 Tolosa-Hunt syndrome (B) can present with painful ophthalmoplegia and multiple cranial neuropathies; however, steroids are typically effective.3 When located along the sphenoid wing, meningiomas (D) can cause multiple progressive cranial neuropathies.4 Typically visible on MRI as extra-axial homogenously enhancing masses,4 no such lesion was observed here. In this patient, the symptomatology, history, and radiographic findings are best explained by PNI of cutaneous squamous cell carcinoma (cSCC), which a biopsy confirmed.One of the most common cancers in the world, cSCC occurs frequently in the head and neck secondary to sun exposure.5 PNI refers to the process of tumor spread into nerves and the space surrounding them.6 An estimated 2% to 6% of patients with cSCC of the head and neck will have PNI.1,6 Cranial nerves V and VII are most commonly involved given their extensive anatomical distributions.1,5,6 Clinically or radiographically apparent PNI confers a poor prognosis with a reported 5-year absolute survival rate of 50%.5Treatment for cSCC of the head and neck includes surgery (if resectable) and high-dose radiotherapy and systemic therapy as appropriate. Immunotherapy with checkpoint inhibition is being used with increasing frequency and notable effectiveness.5-9 Early-phase studies demonstrated impressive response rates near 50% for advanced, unresectable, and metastatic cSCC of the head and neck, earning US Food and Drug Administration approval for 2 checkpoint inhibitors in this setting.7,8 Recently, a landmark phase 2 trial of neoadjuvant cemiplimab for stage II through IV (M0) cSCC before surgery was published, with 51% complete pathological response rates and 68% objective response rates on imaging.9 Similarly, in a recent report of 11 patients with cSCC of the head and neck with clinical PNI treated with checkpoint inhibitors, radiographic disease control was observed in 9 of 11 patients at extended follow-up.5 Many of these responses are durable and curative.The presence of both CN V and VII symptoms in a patient with a history of head and neck cSCC should raise suspicion for perineural recurrence of disease. While initial MRI may be negative, radiographic manifestation of PNI often occurs over time as the disease progresses and symptoms worsen. Expert review by a neuroradiologist can be helpful in identifying this finding earlier in the disease course. Mounting evidence suggests that immunotherapy is a promising treatment option for this population and should be considered as first-line therapy.

Neurology

A 68-year-old patient presented with progressive right-sided facial numbness and weakness, vision changes, and headaches. Their symptoms began 5 years earlier with right temple numbness, which expanded to include the entire right face and mouth. They then developed progressive right facial weakness with a droop, slurred speech, and eyelid ptosis. Finally, binocular vertical and horizontal diplopia and periorbital headaches began. Trials of gabapentin and steroids provided no relief. Their history was significant for a left cheek melanoma completely excised years prior, numerous cutaneous squamous and basal cell carcinomas of the bilateral head and neck removed without issue, type 2 diabetes, and hyperlipidemia. Their medications included metformin and simvastatin; they had no history of smoking or drinking.On examination, they had right-sided ptosis and severe right facial weakness in a lower motor neuron pattern with temporal wasting. The right pupil was fixed and dilated. There was no afferent pupillary defect. The left pupil was appropriately sized and reactive. Their right-sided vision was impaired (20/250) with blurriness. Vertical and horizontal binocular diplopia was present. Right extraocular movements were significantly limited in all directions and painful, and right-sided facial sensation was diminished to pinprick in all cranial nerve (CN) V distributions. Their speech was slightly slurred. Left-sided extraocular movements were intact. Their left facial sensation was intact to pinprick, and their strength was without deficit. There were no other neurological abnormalities.Initial magnetic resonance images (MRIs) were unremarkable. A biopsy of CN VII was nondiagnostic. Hemoglobin A1c was 6.8%. Tests for infection and autoimmune disease had negative results. Cerebrospinal fluid (CSF) studies showed mildly elevated protein values. Figure 1 shows the MRI at presentation.T1 turbo spin-echo fat-saturated magnetic resonance images of the brain through the skull base at presentation.

what is your diagnosis?

What is your diagnosis?

Tolosa-Hunt syndrome

Perineural spread of cutaneous malignancy

Sphenoid wing meningioma

Primary leptomeningeal lymphoma

b

neutral

61-70

augmented_neutral_frommale

https://jamanetwork.com/journals/jamaoncology/fullarticle/2810749

A 31-year-old man presented with left cervical and left inguinal masses. He reported intermittent itching and night sweats for 2 years. He denied fever, weight loss, shortness of breath, rashes, diarrhea, and neurological symptoms. On a preemployment evaluation, the patient was told he had a high white blood cell count 2 years ago. On examination, there was left cervical and inguinal lymphadenopathy and no other organomegaly. Complete blood cell count and peripheral blood smear showed marked leukocytosis, with a white blood cell count of 22 340/μL, an absolute neutrophil count of 5360/μL, and 55% eosinophils with an absolute eosinophil count of 12 290/μL (to convert all to cells ×109/L, multiply by 0.001). Vitamin B12 was markedly elevated at more than 4000 pg/mL (to convert to pmol/L, multiply by 0.7378). The erythrocyte sedimentation rate was 5 mm/h. Lactate dehydrogenase was 180 U/L, and alkaline phosphatase was 81 U/L (to convert both to μkat/L, multiply by 0.0167). Evaluations for HIV and hepatitis B and C were all negative. Serum creatinine was 0.76 mg/dL (to convert to μmol/L, multiply by 88.4); alanine aminotransferase and aspartate aminotransferase were 11 U/L and 9.9 U/L, respectively (to convert to μkat/L, multiply by 0.0167); and total bilirubin was 0.35 mg/dL (to convert to μmol/L, multiply by 17.104). Bone marrow biopsy showed hypercellular marrow (cellularity of 100%), myeloid hyperplasia, increased eosinophils with some dysplasia, and a blast count of 2%. Positron emission tomographic–computed tomographic scan showed a left upper cervical lymph node of 2.6 cm and a left inguinal lymph node of 3.1 × 2.3 cm with an standardized uptake value max of 5.7 (Figure, A). Left inguinal lymph node biopsy showed partial involvement by atypical cells with high proliferation index (Ki-67 >95%) that were positive for CD3, CD4, CD8, BCL2, and TDT, suggestive of T-cell lymphoblastic lymphoma/leukemia (Figure, B).A, Positron emission tomographic–computed tomographic (PET/CT) scan of the head and neck at presentation showing a left upper cervical lymph node of 2.6 cm (arrowhead). B, Lymph node biopsy immunohistochemical stain with terminal deoxynucleotidyl transferase. The inset shows interphase fluorescence in situ hybridization for FIP1L1::PDGFRA rearrangement (positive). C, PET/CT 12 weeks after treatment initiation.Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions What Is Your Diagnosis?

Kimura disease

Classic Hodgkin lymphoma

T-cell acute lymphoblastic lymphoma/leukemia

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

D. Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

D

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

The differential diagnoses in young men with eosinophilia and a neck mass can be wide. The typical presentation of Kimura disease is a painless, unilateral swelling of cervical lymph nodes in young adult male patients with peripheral blood eosinophilia and elevated immunoglobulin E levels. Histological evaluation, however, would show hyperplastic reactive follicles with eosinophilic infiltrates in a background of polymorphous inflammatory cells, a picture inconsistent with the presented case. Although Hodgkin lymphoma can present with eosinophilia and neck mass in young adults, the biopsy was inconsistent with the typical morphology of Reed-Sternberg cells in the background of nonneoplastic inflammatory cells. The diagnosis of T-cell acute lymphoblastic lymphoma/leukemia is reasonable given the morphology from lymph node biopsy; however, in the diagnosis hierarchy, myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) would supersede other myeloid and lymphoid cancers.1In the fifth edition of the World Health Organization Classification of Haematolymphoid Tumours, MLN-TK refers to BCR::ABL1–negative myeloid or lymphoid neoplasms with gene rearrangements leading to an activated tyrosine-kinase domain that results in cell-signaling dysregulation.1 This includes PDGFRA, PDGFRB, FGFR1, JAK2, and FLT3 rearrangements, in addition to ETV6::ABL1, ETV6::FGFR2, ETV6::LYN, ETV6::NTRK3, RANBP2::ALK, BCR::RET, and FGFR1OP::RET fusions.1 An increase in vitamin B12 is often found in patients with PDGFRA and PDGFRB disease.2,3 Most patients are male with chronic myeloid neoplasms with eosinophilia; however, patients rarely present with acute myeloid or T-cell leukemia or extramedullary disease.2Fluorescence in situ hybridization (FISH) was positive for FIP1L1::PDGFRA (4q12) fusion in 91% of nuclei, while karyotype was normal (46, XY in 18 cells), as a cryptic loss of the CHIC2 gene causes this fusion. Next, generation sequencing panel for myeloid neoplasms was negative for variants in targeted regions of the genes commonly involved in myeloid neoplasms. Combining imatinib with chemotherapy is acceptable in patients with acute leukemia or extramedullary diseases, although monotherapy with imatinib has shown promising results.4 The patient was concerned about fertility, as he and his partner were starting a family, and decided to avoid chemotherapy. The patient was concomitantly initiated on 1 mg/kg of prednisone for 7 days and imatinib at 600 mg daily. The eosinophil counts normalized after 2 days, and bone marrow evaluation after 4 weeks showed resolution of eosinophilic infiltration; however, FISH results were 3% positive for FIP1L1::PDGFRA fusion. Repeat bone marrow evaluation after 8 weeks showed complete resolution of the FISH abnormality, and the imatinib dose was reduced to 400 mg daily. Although studies have confirmed deep and durable remission with a starting dose of imatinib, 100 mg, we elected to start with a high dose given the patient’s young age and blastic presentation.5,6 Follow-up positron emission tomographic–computed tomographic scan 12 weeks after initiation of imatinib was consistent with complete metabolic remission (Figure, C). Complete hematological remission is achieved in more than 95% of patients with imatinib and is typically seen early (within weeks of treatment initiation). Cytogenetic/molecular response can be achieved within 3 to 6 months of treatment initiation.7 In patients who achieved molecular remission, the imatinib dose can be reduced to 100 thrice weekly or weekly.8 Treatment-free remission as the experience with chronic myeloid leukemia has been tried, although with limited experience. The success rate is around 60%, with most patients relapsing within the first 10 months. Reinitiating of imatinib restores hematological remission in almost all patients.9,10The current patient was in complete remission 12 months from his treatment and receiving imatinib. Evaluating patients suspected of MLN-TK is critical, as treatment and prognosis may drastically change.

Oncology

A 31-year-old man presented with left cervical and left inguinal masses. He reported intermittent itching and night sweats for 2 years. He denied fever, weight loss, shortness of breath, rashes, diarrhea, and neurological symptoms. On a preemployment evaluation, the patient was told he had a high white blood cell count 2 years ago. On examination, there was left cervical and inguinal lymphadenopathy and no other organomegaly. Complete blood cell count and peripheral blood smear showed marked leukocytosis, with a white blood cell count of 22 340/μL, an absolute neutrophil count of 5360/μL, and 55% eosinophils with an absolute eosinophil count of 12 290/μL (to convert all to cells ×109/L, multiply by 0.001). Vitamin B12 was markedly elevated at more than 4000 pg/mL (to convert to pmol/L, multiply by 0.7378). The erythrocyte sedimentation rate was 5 mm/h. Lactate dehydrogenase was 180 U/L, and alkaline phosphatase was 81 U/L (to convert both to μkat/L, multiply by 0.0167). Evaluations for HIV and hepatitis B and C were all negative. Serum creatinine was 0.76 mg/dL (to convert to μmol/L, multiply by 88.4); alanine aminotransferase and aspartate aminotransferase were 11 U/L and 9.9 U/L, respectively (to convert to μkat/L, multiply by 0.0167); and total bilirubin was 0.35 mg/dL (to convert to μmol/L, multiply by 17.104). Bone marrow biopsy showed hypercellular marrow (cellularity of 100%), myeloid hyperplasia, increased eosinophils with some dysplasia, and a blast count of 2%. Positron emission tomographic–computed tomographic scan showed a left upper cervical lymph node of 2.6 cm and a left inguinal lymph node of 3.1 × 2.3 cm with an standardized uptake value max of 5.7 (Figure, A). Left inguinal lymph node biopsy showed partial involvement by atypical cells with high proliferation index (Ki-67 >95%) that were positive for CD3, CD4, CD8, BCL2, and TDT, suggestive of T-cell lymphoblastic lymphoma/leukemia (Figure, B).A, Positron emission tomographic–computed tomographic (PET/CT) scan of the head and neck at presentation showing a left upper cervical lymph node of 2.6 cm (arrowhead). B, Lymph node biopsy immunohistochemical stain with terminal deoxynucleotidyl transferase. The inset shows interphase fluorescence in situ hybridization for FIP1L1::PDGFRA rearrangement (positive). C, PET/CT 12 weeks after treatment initiation.Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

what is your diagnosis?

What is your diagnosis?

T-cell acute lymphoblastic lymphoma/leukemia

Kimura disease

Classic Hodgkin lymphoma

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

d

male

31-40

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2810749

A 31-year-old man presented with left cervical and left inguinal masses. He reported intermittent itching and night sweats for 2 years. He denied fever, weight loss, shortness of breath, rashes, diarrhea, and neurological symptoms. On a preemployment evaluation, the patient was told he had a high white blood cell count 2 years ago. On examination, there was left cervical and inguinal lymphadenopathy and no other organomegaly. Complete blood cell count and peripheral blood smear showed marked leukocytosis, with a white blood cell count of 22 340/μL, an absolute neutrophil count of 5360/μL, and 55% eosinophils with an absolute eosinophil count of 12 290/μL (to convert all to cells ×109/L, multiply by 0.001). Vitamin B12 was markedly elevated at more than 4000 pg/mL (to convert to pmol/L, multiply by 0.7378). The erythrocyte sedimentation rate was 5 mm/h. Lactate dehydrogenase was 180 U/L, and alkaline phosphatase was 81 U/L (to convert both to μkat/L, multiply by 0.0167). Evaluations for HIV and hepatitis B and C were all negative. Serum creatinine was 0.76 mg/dL (to convert to μmol/L, multiply by 88.4); alanine aminotransferase and aspartate aminotransferase were 11 U/L and 9.9 U/L, respectively (to convert to μkat/L, multiply by 0.0167); and total bilirubin was 0.35 mg/dL (to convert to μmol/L, multiply by 17.104). Bone marrow biopsy showed hypercellular marrow (cellularity of 100%), myeloid hyperplasia, increased eosinophils with some dysplasia, and a blast count of 2%. Positron emission tomographic–computed tomographic scan showed a left upper cervical lymph node of 2.6 cm and a left inguinal lymph node of 3.1 × 2.3 cm with an standardized uptake value max of 5.7 (Figure, A). Left inguinal lymph node biopsy showed partial involvement by atypical cells with high proliferation index (Ki-67 >95%) that were positive for CD3, CD4, CD8, BCL2, and TDT, suggestive of T-cell lymphoblastic lymphoma/leukemia (Figure, B).A, Positron emission tomographic–computed tomographic (PET/CT) scan of the head and neck at presentation showing a left upper cervical lymph node of 2.6 cm (arrowhead). B, Lymph node biopsy immunohistochemical stain with terminal deoxynucleotidyl transferase. The inset shows interphase fluorescence in situ hybridization for FIP1L1::PDGFRA rearrangement (positive). C, PET/CT 12 weeks after treatment initiation.Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions What Is Your Diagnosis?

Kimura disease

Classic Hodgkin lymphoma

T-cell acute lymphoblastic lymphoma/leukemia

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

D. Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

D

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

The differential diagnoses in young men with eosinophilia and a neck mass can be wide. The typical presentation of Kimura disease is a painless, unilateral swelling of cervical lymph nodes in young adult male patients with peripheral blood eosinophilia and elevated immunoglobulin E levels. Histological evaluation, however, would show hyperplastic reactive follicles with eosinophilic infiltrates in a background of polymorphous inflammatory cells, a picture inconsistent with the presented case. Although Hodgkin lymphoma can present with eosinophilia and neck mass in young adults, the biopsy was inconsistent with the typical morphology of Reed-Sternberg cells in the background of nonneoplastic inflammatory cells. The diagnosis of T-cell acute lymphoblastic lymphoma/leukemia is reasonable given the morphology from lymph node biopsy; however, in the diagnosis hierarchy, myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) would supersede other myeloid and lymphoid cancers.1In the fifth edition of the World Health Organization Classification of Haematolymphoid Tumours, MLN-TK refers to BCR::ABL1–negative myeloid or lymphoid neoplasms with gene rearrangements leading to an activated tyrosine-kinase domain that results in cell-signaling dysregulation.1 This includes PDGFRA, PDGFRB, FGFR1, JAK2, and FLT3 rearrangements, in addition to ETV6::ABL1, ETV6::FGFR2, ETV6::LYN, ETV6::NTRK3, RANBP2::ALK, BCR::RET, and FGFR1OP::RET fusions.1 An increase in vitamin B12 is often found in patients with PDGFRA and PDGFRB disease.2,3 Most patients are male with chronic myeloid neoplasms with eosinophilia; however, patients rarely present with acute myeloid or T-cell leukemia or extramedullary disease.2Fluorescence in situ hybridization (FISH) was positive for FIP1L1::PDGFRA (4q12) fusion in 91% of nuclei, while karyotype was normal (46, XY in 18 cells), as a cryptic loss of the CHIC2 gene causes this fusion. Next, generation sequencing panel for myeloid neoplasms was negative for variants in targeted regions of the genes commonly involved in myeloid neoplasms. Combining imatinib with chemotherapy is acceptable in patients with acute leukemia or extramedullary diseases, although monotherapy with imatinib has shown promising results.4 The patient was concerned about fertility, as he and his partner were starting a family, and decided to avoid chemotherapy. The patient was concomitantly initiated on 1 mg/kg of prednisone for 7 days and imatinib at 600 mg daily. The eosinophil counts normalized after 2 days, and bone marrow evaluation after 4 weeks showed resolution of eosinophilic infiltration; however, FISH results were 3% positive for FIP1L1::PDGFRA fusion. Repeat bone marrow evaluation after 8 weeks showed complete resolution of the FISH abnormality, and the imatinib dose was reduced to 400 mg daily. Although studies have confirmed deep and durable remission with a starting dose of imatinib, 100 mg, we elected to start with a high dose given the patient’s young age and blastic presentation.5,6 Follow-up positron emission tomographic–computed tomographic scan 12 weeks after initiation of imatinib was consistent with complete metabolic remission (Figure, C). Complete hematological remission is achieved in more than 95% of patients with imatinib and is typically seen early (within weeks of treatment initiation). Cytogenetic/molecular response can be achieved within 3 to 6 months of treatment initiation.7 In patients who achieved molecular remission, the imatinib dose can be reduced to 100 thrice weekly or weekly.8 Treatment-free remission as the experience with chronic myeloid leukemia has been tried, although with limited experience. The success rate is around 60%, with most patients relapsing within the first 10 months. Reinitiating of imatinib restores hematological remission in almost all patients.9,10The current patient was in complete remission 12 months from his treatment and receiving imatinib. Evaluating patients suspected of MLN-TK is critical, as treatment and prognosis may drastically change.

Oncology

A 31-year-old woman presented with left cervical and left inguinal masses. She reported intermittent itching and night sweats for 2 years. She denied fever, weight loss, shortness of breath, rashes, diarrhea, and neurological symptoms. On a preemployment evaluation, the woman was told she had a high white blood cell count 2 years ago. On examination, there was left cervical and inguinal lymphadenopathy and no other organomegaly. Complete blood cell count and peripheral blood smear showed marked leukocytosis, with a white blood cell count of 22 340/μL, an absolute neutrophil count of 5360/μL, and 55% eosinophils with an absolute eosinophil count of 12 290/μL (to convert all to cells ×109/L, multiply by 0.001). Vitamin B12 was markedly elevated at more than 4000 pg/mL (to convert to pmol/L, multiply by 0.7378). The erythrocyte sedimentation rate was 5 mm/h. Lactate dehydrogenase was 180 U/L, and alkaline phosphatase was 81 U/L (to convert both to μkat/L, multiply by 0.0167). Evaluations for HIV and hepatitis B and C were all negative. Serum creatinine was 0.76 mg/dL (to convert to μmol/L, multiply by 88.4); alanine aminotransferase and aspartate aminotransferase were 11 U/L and 9.9 U/L, respectively (to convert to μkat/L, multiply by 0.0167); and total bilirubin was 0.35 mg/dL (to convert to μmol/L, multiply by 17.104). Bone marrow biopsy showed hypercellular marrow (cellularity of 100%), myeloid hyperplasia, increased eosinophils with some dysplasia, and a blast count of 2%. Positron emission tomographic–computed tomographic scan showed a left upper cervical lymph node of 2.6 cm and a left inguinal lymph node of 3.1 × 2.3 cm with an standardized uptake value max of 5.7 (Figure, A). Left inguinal lymph node biopsy showed partial involvement by atypical cells with high proliferation index (Ki-67 >95%) that were positive for CD3, CD4, CD8, BCL2, and TDT, suggestive of T-cell lymphoblastic lymphoma/leukemia (Figure, B).A, Positron emission tomographic–computed tomographic (PET/CT) scan of the head and neck at presentation showing a left upper cervical lymph node of 2.6 cm (arrowhead). B, Lymph node biopsy immunohistochemical stain with terminal deoxynucleotidyl transferase. The inset shows interphase fluorescence in situ hybridization for FIP1L1::PDGFRA rearrangement (positive). C, PET/CT 12 weeks after treatment initiation.Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

what is your diagnosis?

What is your diagnosis?

T-cell acute lymphoblastic lymphoma/leukemia

Kimura disease

Classic Hodgkin lymphoma

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

d

female

31-40

White

augmented_female_frommale

https://jamanetwork.com/journals/jamaoncology/fullarticle/2810749

A 31-year-old man presented with left cervical and left inguinal masses. He reported intermittent itching and night sweats for 2 years. He denied fever, weight loss, shortness of breath, rashes, diarrhea, and neurological symptoms. On a preemployment evaluation, the patient was told he had a high white blood cell count 2 years ago. On examination, there was left cervical and inguinal lymphadenopathy and no other organomegaly. Complete blood cell count and peripheral blood smear showed marked leukocytosis, with a white blood cell count of 22 340/μL, an absolute neutrophil count of 5360/μL, and 55% eosinophils with an absolute eosinophil count of 12 290/μL (to convert all to cells ×109/L, multiply by 0.001). Vitamin B12 was markedly elevated at more than 4000 pg/mL (to convert to pmol/L, multiply by 0.7378). The erythrocyte sedimentation rate was 5 mm/h. Lactate dehydrogenase was 180 U/L, and alkaline phosphatase was 81 U/L (to convert both to μkat/L, multiply by 0.0167). Evaluations for HIV and hepatitis B and C were all negative. Serum creatinine was 0.76 mg/dL (to convert to μmol/L, multiply by 88.4); alanine aminotransferase and aspartate aminotransferase were 11 U/L and 9.9 U/L, respectively (to convert to μkat/L, multiply by 0.0167); and total bilirubin was 0.35 mg/dL (to convert to μmol/L, multiply by 17.104). Bone marrow biopsy showed hypercellular marrow (cellularity of 100%), myeloid hyperplasia, increased eosinophils with some dysplasia, and a blast count of 2%. Positron emission tomographic–computed tomographic scan showed a left upper cervical lymph node of 2.6 cm and a left inguinal lymph node of 3.1 × 2.3 cm with an standardized uptake value max of 5.7 (Figure, A). Left inguinal lymph node biopsy showed partial involvement by atypical cells with high proliferation index (Ki-67 >95%) that were positive for CD3, CD4, CD8, BCL2, and TDT, suggestive of T-cell lymphoblastic lymphoma/leukemia (Figure, B).A, Positron emission tomographic–computed tomographic (PET/CT) scan of the head and neck at presentation showing a left upper cervical lymph node of 2.6 cm (arrowhead). B, Lymph node biopsy immunohistochemical stain with terminal deoxynucleotidyl transferase. The inset shows interphase fluorescence in situ hybridization for FIP1L1::PDGFRA rearrangement (positive). C, PET/CT 12 weeks after treatment initiation.Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions What Is Your Diagnosis?

Kimura disease

Classic Hodgkin lymphoma

T-cell acute lymphoblastic lymphoma/leukemia

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

D. Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

D

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

The differential diagnoses in young men with eosinophilia and a neck mass can be wide. The typical presentation of Kimura disease is a painless, unilateral swelling of cervical lymph nodes in young adult male patients with peripheral blood eosinophilia and elevated immunoglobulin E levels. Histological evaluation, however, would show hyperplastic reactive follicles with eosinophilic infiltrates in a background of polymorphous inflammatory cells, a picture inconsistent with the presented case. Although Hodgkin lymphoma can present with eosinophilia and neck mass in young adults, the biopsy was inconsistent with the typical morphology of Reed-Sternberg cells in the background of nonneoplastic inflammatory cells. The diagnosis of T-cell acute lymphoblastic lymphoma/leukemia is reasonable given the morphology from lymph node biopsy; however, in the diagnosis hierarchy, myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) would supersede other myeloid and lymphoid cancers.1In the fifth edition of the World Health Organization Classification of Haematolymphoid Tumours, MLN-TK refers to BCR::ABL1–negative myeloid or lymphoid neoplasms with gene rearrangements leading to an activated tyrosine-kinase domain that results in cell-signaling dysregulation.1 This includes PDGFRA, PDGFRB, FGFR1, JAK2, and FLT3 rearrangements, in addition to ETV6::ABL1, ETV6::FGFR2, ETV6::LYN, ETV6::NTRK3, RANBP2::ALK, BCR::RET, and FGFR1OP::RET fusions.1 An increase in vitamin B12 is often found in patients with PDGFRA and PDGFRB disease.2,3 Most patients are male with chronic myeloid neoplasms with eosinophilia; however, patients rarely present with acute myeloid or T-cell leukemia or extramedullary disease.2Fluorescence in situ hybridization (FISH) was positive for FIP1L1::PDGFRA (4q12) fusion in 91% of nuclei, while karyotype was normal (46, XY in 18 cells), as a cryptic loss of the CHIC2 gene causes this fusion. Next, generation sequencing panel for myeloid neoplasms was negative for variants in targeted regions of the genes commonly involved in myeloid neoplasms. Combining imatinib with chemotherapy is acceptable in patients with acute leukemia or extramedullary diseases, although monotherapy with imatinib has shown promising results.4 The patient was concerned about fertility, as he and his partner were starting a family, and decided to avoid chemotherapy. The patient was concomitantly initiated on 1 mg/kg of prednisone for 7 days and imatinib at 600 mg daily. The eosinophil counts normalized after 2 days, and bone marrow evaluation after 4 weeks showed resolution of eosinophilic infiltration; however, FISH results were 3% positive for FIP1L1::PDGFRA fusion. Repeat bone marrow evaluation after 8 weeks showed complete resolution of the FISH abnormality, and the imatinib dose was reduced to 400 mg daily. Although studies have confirmed deep and durable remission with a starting dose of imatinib, 100 mg, we elected to start with a high dose given the patient’s young age and blastic presentation.5,6 Follow-up positron emission tomographic–computed tomographic scan 12 weeks after initiation of imatinib was consistent with complete metabolic remission (Figure, C). Complete hematological remission is achieved in more than 95% of patients with imatinib and is typically seen early (within weeks of treatment initiation). Cytogenetic/molecular response can be achieved within 3 to 6 months of treatment initiation.7 In patients who achieved molecular remission, the imatinib dose can be reduced to 100 thrice weekly or weekly.8 Treatment-free remission as the experience with chronic myeloid leukemia has been tried, although with limited experience. The success rate is around 60%, with most patients relapsing within the first 10 months. Reinitiating of imatinib restores hematological remission in almost all patients.9,10The current patient was in complete remission 12 months from his treatment and receiving imatinib. Evaluating patients suspected of MLN-TK is critical, as treatment and prognosis may drastically change.

Oncology

A 31-year-old patient presented with left cervical and left inguinal masses. They reported intermittent itching and night sweats for 2 years. They denied fever, weight loss, shortness of breath, rashes, diarrhea, and neurological symptoms. On a preemployment evaluation, the patient was told they had a high white blood cell count 2 years ago. On examination, there was left cervical and inguinal lymphadenopathy and no other organomegaly. Complete blood cell count and peripheral blood smear showed marked leukocytosis, with a white blood cell count of 22 340/μL, an absolute neutrophil count of 5360/μL, and 55% eosinophils with an absolute eosinophil count of 12 290/μL (to convert all to cells ×109/L, multiply by 0.001). Vitamin B12 was markedly elevated at more than 4000 pg/mL (to convert to pmol/L, multiply by 0.7378). The erythrocyte sedimentation rate was 5 mm/h. Lactate dehydrogenase was 180 U/L, and alkaline phosphatase was 81 U/L (to convert both to μkat/L, multiply by 0.0167). Evaluations for HIV and hepatitis B and C were all negative. Serum creatinine was 0.76 mg/dL (to convert to μmol/L, multiply by 88.4); alanine aminotransferase and aspartate aminotransferase were 11 U/L and 9.9 U/L, respectively (to convert to μkat/L, multiply by 0.0167); and total bilirubin was 0.35 mg/dL (to convert to μmol/L, multiply by 17.104). Bone marrow biopsy showed hypercellular marrow (cellularity of 100%), myeloid hyperplasia, increased eosinophils with some dysplasia, and a blast count of 2%. Positron emission tomographic–computed tomographic scan showed a left upper cervical lymph node of 2.6 cm and a left inguinal lymph node of 3.1 × 2.3 cm with an standardized uptake value max of 5.7 (Figure, A). Left inguinal lymph node biopsy showed partial involvement by atypical cells with high proliferation index (Ki-67 >95%) that were positive for CD3, CD4, CD8, BCL2, and TDT, suggestive of T-cell lymphoblastic lymphoma/leukemia (Figure, B).A, Positron emission tomographic–computed tomographic (PET/CT) scan of the head and neck at presentation showing a left upper cervical lymph node of 2.6 cm (arrowhead). B, Lymph node biopsy immunohistochemical stain with terminal deoxynucleotidyl transferase. The inset shows interphase fluorescence in situ hybridization for FIP1L1::PDGFRA rearrangement (positive). C, PET/CT 12 weeks after treatment initiation.Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

what is your diagnosis?

What is your diagnosis?

T-cell acute lymphoblastic lymphoma/leukemia

Kimura disease

Classic Hodgkin lymphoma

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

d

neutral

31-40

White

augmented_neutral_frommale

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2810850

A 28-year-old woman presented with a 5-day history of painful cervical lymphadenopathy along with fever, nausea, and vomiting. Treatment with antibiotics and corticosteroids was started, without improvement of symptoms. She denied recent travel, sick contacts, or autoimmune disease. Her medical history was significant for α-thalassemia but otherwise noncontributory.On examination, she had tender lymphadenopathy involving right level V. A computed tomography scan of the neck revealed a collection of enlarged, matted nodes without evidence of an abscess. Fine-needle aspiration (FNA) biopsy showed nondiagnostic reactive lymph nodes. She was subsequently admitted to the hospital, where the lymphadenopathy progressed to the left side of the neck and a skin eruption developed over her face, back, and trunk. Results of an infectious disease and rheumatological workup, including bone marrow biopsy, were negative. Given her persistent symptoms, the ear, nose, and throat service consulted for excisional biopsy.On pathologic examination, the lymph nodes showed extensive coagulative necrosis, apoptosis, and karyorrhectic debris (Figure 1). Cellular components included histiocytes and dendritic cells, with absent neutrophils and hematoxylin bodies.Well-defined areas of fibrinoid necrosis in paracortical areas (hematoxylin-eosin, original magnification ×20). What Is Your Diagnosis?

Lymphoma

Kikuchi-Fujimoto disease

Systemic lupus erythematosus

Rosai-Dorfman disease

B. Kikuchi-Fujimoto disease

B

Kikuchi-Fujimoto disease

Common diagnostic considerations of lymphadenopathy alongside recurrent fever in young adults include infection, autoimmune disorders, and malignant neoplasms. Failure of conservative management with antibiotics reduces the likelihood of bacterial infection, whereas lack of cutaneous findings is atypical for a patient with classic systemic lupus erythematosus (SLE) (option C). Furthermore, both FNA and bone marrow biopsy results were not concerning for malignancy. Due to her relatively nonspecific and persistent symptoms, excisional biopsy was performed, giving the final diagnosis of Kikuchi-Fujimoto disease (KFD).Kikuchi-Fujimoto disease (also known as Kikuchi-Fujimoto lymphadenopathy, Kikuchi lymphadenitis, and necrotizing lymphadenitis of unknown etiology) is a benign, self-limiting disease that commonly affects young adults. This rare disease was first reported in Japan in 1972, with the highest prevalence in Asia.1 Patients typically present with painful cervical lymphadenopathy alongside fever and leukopenia.2 It commonly affects women younger than 40 years. Recent studies, however, suggest a more equal distribution among men and women.3Although the etiology is unknown, both autoimmune and viral causes are suspected. Involvement of Epstein-Barr and other herpesviruses is controversial and can be distinguished with periodic acid–Schiff, Grocott methenamine silver, and Ziehl-Nielsen stains. An inappropriate immune reaction has been hypothesized, as KFD is a T-cell–mediated response in those with a specific genetic profile.3 Individuals with KFD have a significantly higher incidence of human leukocyte antigen class II genes (specifically, the DPA1*01 and DPB1*0202 alleles, which are more common in Asian individuals).3 Interestingly, KFD has also occurred in conjunction with SLE, preceding its onset in 30% of cases.4The FNA biopsy is not specific in diagnosing KFD, with an accuracy of 56.7%.5 Therefore, excisional biopsy of the affected lymph nodes is often required. Figure 1 shows a typical necrotic phase of Kikuchi lymphadenitis with well-defined areas of fibrinoid necrosis in paracortical areas of affected lymph nodes. The necrotic foci show abundant karyorrhectic and cellular debris, fibrin deposition, and mononuclear cells (Figure 2). There are no intact neutrophils or eosinophils and only rare plasma cells. Crescentic histiocytes with phagocytized debris are seen along with numerous plasmacytoid dendritic cells/monocytes, macrophages, and activated T cells, which can simulate the appearance of a peripheral T-cell lymphoma. Some cases show prominent xanthomatous inflammation with foamy histiocytes.The necrotic foci show abundant karyorrhectic and cellular debris, fibrin deposition, and mononuclear cells. There are no intact neutrophils or eosinophils and only rare plasma cells. Crescentic histiocytes with phagocytized debris as well as plasmacytoid dendritic cells/monocytes are seen (hematoxylin-eosin, original magnification ×100).This disease is self-limited, lasting 1 to 4 months; although recurrence has been reported, the incidence is 3% to 4%.3 The fatality rate is low and has been reported in only 3 patients. Treatment is largely supportive with analgesic agents, antipyretic agents, and corticosteroids. In patients with recurrent symptoms, low doses of corticosteroids may achieve remission.6The differential diagnosis includes lymphoma with necrosis (option A), cat-scratch disease, and lupus lymphadenitis. Cat-scratch disease is confirmed by serologic testing for Bartonella henselae antibodies.5 Patients with lupus present with lymphadenopathy, fever, skin eruption, and hepatosplenomegaly. In contrast, patients with KFD present with predominantly cervical lymphadenopathy alongside fever and skin eruption.6 Although nonspecific, serologic testing may show leukopenia, anemia, thrombocytopenia, or atypical lymphocytes on peripheral blood smear.At last follow-up, this patient’s fever and lymphadenopathy had resolved, but the skin eruption had progressed to her hands and feet. She is currently receiving prednisone therapy and undergoing an autoimmune workup due to high suspicion of disease progression to SLE or myositis. She will continue to follow up with rheumatology, hematology/oncology, infectious disease, and otolaryngology services.

General

A 28-year-old woman presented with a 5-day history of painful cervical lymphadenopathy along with fever, nausea, and vomiting. Treatment with antibiotics and corticosteroids was started, without improvement of symptoms. She denied recent travel, sick contacts, or autoimmune disease. Her medical history was significant for α-thalassemia but otherwise noncontributory.On examination, she had tender lymphadenopathy involving right level V. A computed tomography scan of the neck revealed a collection of enlarged, matted nodes without evidence of an abscess. Fine-needle aspiration (FNA) biopsy showed nondiagnostic reactive lymph nodes. She was subsequently admitted to the hospital, where the lymphadenopathy progressed to the left side of the neck and a skin eruption developed over her face, back, and trunk. Results of an infectious disease and rheumatological workup, including bone marrow biopsy, were negative. Given her persistent symptoms, the ear, nose, and throat service consulted for excisional biopsy.On pathologic examination, the lymph nodes showed extensive coagulative necrosis, apoptosis, and karyorrhectic debris (Figure 1). Cellular components included histiocytes and dendritic cells, with absent neutrophils and hematoxylin bodies.Well-defined areas of fibrinoid necrosis in paracortical areas (hematoxylin-eosin, original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Lymphoma

Systemic lupus erythematosus

Kikuchi-Fujimoto disease

Rosai-Dorfman disease

c

female

21-30

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2810850

A 28-year-old woman presented with a 5-day history of painful cervical lymphadenopathy along with fever, nausea, and vomiting. Treatment with antibiotics and corticosteroids was started, without improvement of symptoms. She denied recent travel, sick contacts, or autoimmune disease. Her medical history was significant for α-thalassemia but otherwise noncontributory.On examination, she had tender lymphadenopathy involving right level V. A computed tomography scan of the neck revealed a collection of enlarged, matted nodes without evidence of an abscess. Fine-needle aspiration (FNA) biopsy showed nondiagnostic reactive lymph nodes. She was subsequently admitted to the hospital, where the lymphadenopathy progressed to the left side of the neck and a skin eruption developed over her face, back, and trunk. Results of an infectious disease and rheumatological workup, including bone marrow biopsy, were negative. Given her persistent symptoms, the ear, nose, and throat service consulted for excisional biopsy.On pathologic examination, the lymph nodes showed extensive coagulative necrosis, apoptosis, and karyorrhectic debris (Figure 1). Cellular components included histiocytes and dendritic cells, with absent neutrophils and hematoxylin bodies.Well-defined areas of fibrinoid necrosis in paracortical areas (hematoxylin-eosin, original magnification ×20). What Is Your Diagnosis?

Lymphoma

Kikuchi-Fujimoto disease

Systemic lupus erythematosus

Rosai-Dorfman disease

B. Kikuchi-Fujimoto disease

B

Kikuchi-Fujimoto disease

Common diagnostic considerations of lymphadenopathy alongside recurrent fever in young adults include infection, autoimmune disorders, and malignant neoplasms. Failure of conservative management with antibiotics reduces the likelihood of bacterial infection, whereas lack of cutaneous findings is atypical for a patient with classic systemic lupus erythematosus (SLE) (option C). Furthermore, both FNA and bone marrow biopsy results were not concerning for malignancy. Due to her relatively nonspecific and persistent symptoms, excisional biopsy was performed, giving the final diagnosis of Kikuchi-Fujimoto disease (KFD).Kikuchi-Fujimoto disease (also known as Kikuchi-Fujimoto lymphadenopathy, Kikuchi lymphadenitis, and necrotizing lymphadenitis of unknown etiology) is a benign, self-limiting disease that commonly affects young adults. This rare disease was first reported in Japan in 1972, with the highest prevalence in Asia.1 Patients typically present with painful cervical lymphadenopathy alongside fever and leukopenia.2 It commonly affects women younger than 40 years. Recent studies, however, suggest a more equal distribution among men and women.3Although the etiology is unknown, both autoimmune and viral causes are suspected. Involvement of Epstein-Barr and other herpesviruses is controversial and can be distinguished with periodic acid–Schiff, Grocott methenamine silver, and Ziehl-Nielsen stains. An inappropriate immune reaction has been hypothesized, as KFD is a T-cell–mediated response in those with a specific genetic profile.3 Individuals with KFD have a significantly higher incidence of human leukocyte antigen class II genes (specifically, the DPA1*01 and DPB1*0202 alleles, which are more common in Asian individuals).3 Interestingly, KFD has also occurred in conjunction with SLE, preceding its onset in 30% of cases.4The FNA biopsy is not specific in diagnosing KFD, with an accuracy of 56.7%.5 Therefore, excisional biopsy of the affected lymph nodes is often required. Figure 1 shows a typical necrotic phase of Kikuchi lymphadenitis with well-defined areas of fibrinoid necrosis in paracortical areas of affected lymph nodes. The necrotic foci show abundant karyorrhectic and cellular debris, fibrin deposition, and mononuclear cells (Figure 2). There are no intact neutrophils or eosinophils and only rare plasma cells. Crescentic histiocytes with phagocytized debris are seen along with numerous plasmacytoid dendritic cells/monocytes, macrophages, and activated T cells, which can simulate the appearance of a peripheral T-cell lymphoma. Some cases show prominent xanthomatous inflammation with foamy histiocytes.The necrotic foci show abundant karyorrhectic and cellular debris, fibrin deposition, and mononuclear cells. There are no intact neutrophils or eosinophils and only rare plasma cells. Crescentic histiocytes with phagocytized debris as well as plasmacytoid dendritic cells/monocytes are seen (hematoxylin-eosin, original magnification ×100).This disease is self-limited, lasting 1 to 4 months; although recurrence has been reported, the incidence is 3% to 4%.3 The fatality rate is low and has been reported in only 3 patients. Treatment is largely supportive with analgesic agents, antipyretic agents, and corticosteroids. In patients with recurrent symptoms, low doses of corticosteroids may achieve remission.6The differential diagnosis includes lymphoma with necrosis (option A), cat-scratch disease, and lupus lymphadenitis. Cat-scratch disease is confirmed by serologic testing for Bartonella henselae antibodies.5 Patients with lupus present with lymphadenopathy, fever, skin eruption, and hepatosplenomegaly. In contrast, patients with KFD present with predominantly cervical lymphadenopathy alongside fever and skin eruption.6 Although nonspecific, serologic testing may show leukopenia, anemia, thrombocytopenia, or atypical lymphocytes on peripheral blood smear.At last follow-up, this patient’s fever and lymphadenopathy had resolved, but the skin eruption had progressed to her hands and feet. She is currently receiving prednisone therapy and undergoing an autoimmune workup due to high suspicion of disease progression to SLE or myositis. She will continue to follow up with rheumatology, hematology/oncology, infectious disease, and otolaryngology services.

General

A 28-year-old man presented with a 5-day history of painful cervical lymphadenopathy along with fever, nausea, and vomiting. Treatment with antibiotics and corticosteroids was started, without improvement of symptoms. He denied recent travel, sick contacts, or autoimmune disease. Him medical history was significant for α-thalassemia but otherwise noncontributory.On examination, he had tender lymphadenopathy involving right level V. A computed tomography scan of the neck revealed a collection of enlarged, matted nodes without evidence of an abscess. Fine-needle aspiration (FNA) biopsy showed nondiagnostic reactive lymph nodes. He was subsequently admitted to the hospital, where the lymphadenopathy progressed to the left side of the neck and a skin eruption developed over him face, back, and trunk. Results of an infectious disease and rheumatological workup, including bone marrow biopsy, were negative. Given him persistent symptoms, the ear, nose, and throat service consulted for excisional biopsy.On pathologic examination, the lymph nodes showed extensive coagulative necrosis, apoptosis, and karyorrhectic debris (Figure 1). Cellular components included histiocytes and dendritic cells, with absent neutrophils and hematoxylin bodies.Well-defined areas of fibrinoid necrosis in paracortical areas (hematoxylin-eosin, original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Lymphoma

Systemic lupus erythematosus

Kikuchi-Fujimoto disease

Rosai-Dorfman disease

c

male

21-30

augmented_male_fromfemale

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2810850

A 28-year-old woman presented with a 5-day history of painful cervical lymphadenopathy along with fever, nausea, and vomiting. Treatment with antibiotics and corticosteroids was started, without improvement of symptoms. She denied recent travel, sick contacts, or autoimmune disease. Her medical history was significant for α-thalassemia but otherwise noncontributory.On examination, she had tender lymphadenopathy involving right level V. A computed tomography scan of the neck revealed a collection of enlarged, matted nodes without evidence of an abscess. Fine-needle aspiration (FNA) biopsy showed nondiagnostic reactive lymph nodes. She was subsequently admitted to the hospital, where the lymphadenopathy progressed to the left side of the neck and a skin eruption developed over her face, back, and trunk. Results of an infectious disease and rheumatological workup, including bone marrow biopsy, were negative. Given her persistent symptoms, the ear, nose, and throat service consulted for excisional biopsy.On pathologic examination, the lymph nodes showed extensive coagulative necrosis, apoptosis, and karyorrhectic debris (Figure 1). Cellular components included histiocytes and dendritic cells, with absent neutrophils and hematoxylin bodies.Well-defined areas of fibrinoid necrosis in paracortical areas (hematoxylin-eosin, original magnification ×20). What Is Your Diagnosis?

Lymphoma

Kikuchi-Fujimoto disease

Systemic lupus erythematosus

Rosai-Dorfman disease

B. Kikuchi-Fujimoto disease

B

Kikuchi-Fujimoto disease

Common diagnostic considerations of lymphadenopathy alongside recurrent fever in young adults include infection, autoimmune disorders, and malignant neoplasms. Failure of conservative management with antibiotics reduces the likelihood of bacterial infection, whereas lack of cutaneous findings is atypical for a patient with classic systemic lupus erythematosus (SLE) (option C). Furthermore, both FNA and bone marrow biopsy results were not concerning for malignancy. Due to her relatively nonspecific and persistent symptoms, excisional biopsy was performed, giving the final diagnosis of Kikuchi-Fujimoto disease (KFD).Kikuchi-Fujimoto disease (also known as Kikuchi-Fujimoto lymphadenopathy, Kikuchi lymphadenitis, and necrotizing lymphadenitis of unknown etiology) is a benign, self-limiting disease that commonly affects young adults. This rare disease was first reported in Japan in 1972, with the highest prevalence in Asia.1 Patients typically present with painful cervical lymphadenopathy alongside fever and leukopenia.2 It commonly affects women younger than 40 years. Recent studies, however, suggest a more equal distribution among men and women.3Although the etiology is unknown, both autoimmune and viral causes are suspected. Involvement of Epstein-Barr and other herpesviruses is controversial and can be distinguished with periodic acid–Schiff, Grocott methenamine silver, and Ziehl-Nielsen stains. An inappropriate immune reaction has been hypothesized, as KFD is a T-cell–mediated response in those with a specific genetic profile.3 Individuals with KFD have a significantly higher incidence of human leukocyte antigen class II genes (specifically, the DPA1*01 and DPB1*0202 alleles, which are more common in Asian individuals).3 Interestingly, KFD has also occurred in conjunction with SLE, preceding its onset in 30% of cases.4The FNA biopsy is not specific in diagnosing KFD, with an accuracy of 56.7%.5 Therefore, excisional biopsy of the affected lymph nodes is often required. Figure 1 shows a typical necrotic phase of Kikuchi lymphadenitis with well-defined areas of fibrinoid necrosis in paracortical areas of affected lymph nodes. The necrotic foci show abundant karyorrhectic and cellular debris, fibrin deposition, and mononuclear cells (Figure 2). There are no intact neutrophils or eosinophils and only rare plasma cells. Crescentic histiocytes with phagocytized debris are seen along with numerous plasmacytoid dendritic cells/monocytes, macrophages, and activated T cells, which can simulate the appearance of a peripheral T-cell lymphoma. Some cases show prominent xanthomatous inflammation with foamy histiocytes.The necrotic foci show abundant karyorrhectic and cellular debris, fibrin deposition, and mononuclear cells. There are no intact neutrophils or eosinophils and only rare plasma cells. Crescentic histiocytes with phagocytized debris as well as plasmacytoid dendritic cells/monocytes are seen (hematoxylin-eosin, original magnification ×100).This disease is self-limited, lasting 1 to 4 months; although recurrence has been reported, the incidence is 3% to 4%.3 The fatality rate is low and has been reported in only 3 patients. Treatment is largely supportive with analgesic agents, antipyretic agents, and corticosteroids. In patients with recurrent symptoms, low doses of corticosteroids may achieve remission.6The differential diagnosis includes lymphoma with necrosis (option A), cat-scratch disease, and lupus lymphadenitis. Cat-scratch disease is confirmed by serologic testing for Bartonella henselae antibodies.5 Patients with lupus present with lymphadenopathy, fever, skin eruption, and hepatosplenomegaly. In contrast, patients with KFD present with predominantly cervical lymphadenopathy alongside fever and skin eruption.6 Although nonspecific, serologic testing may show leukopenia, anemia, thrombocytopenia, or atypical lymphocytes on peripheral blood smear.At last follow-up, this patient’s fever and lymphadenopathy had resolved, but the skin eruption had progressed to her hands and feet. She is currently receiving prednisone therapy and undergoing an autoimmune workup due to high suspicion of disease progression to SLE or myositis. She will continue to follow up with rheumatology, hematology/oncology, infectious disease, and otolaryngology services.

General

A 28-year-old patient presented with a 5-day history of painful cervical lymphadenopathy along with fever, nausea, and vomiting. Treatment with antibiotics and corticosteroids was started, without improvement of symptoms. They denied recent travel, sick contacts, or autoimmune disease. Them medical history was significant for α-thalassemia but otherwise noncontributory.On examination, they had tender lymphadenopathy involving right level V. A computed tomography scan of the neck revealed a collection of enlarged, matted nodes without evidence of an abscess. Fine-needle aspiration (FNA) biopsy showed nondiagnostic reactive lymph nodes. They was subsequently admitted to the hospital, where the lymphadenopathy progressed to the left side of the neck and a skin eruption developed over them face, back, and trunk. Results of an infectious disease and rheumatological workup, including bone marrow biopsy, were negative. Given them persistent symptoms, the ear, nose, and throat service consulted for excisional biopsy.On pathologic examination, the lymph nodes showed extensive coagulative necrosis, apoptosis, and karyorrhectic debris (Figure 1). Cellular components included histiocytes and dendritic cells, with absent neutrophils and hematoxylin bodies.Well-defined areas of fibrinoid necrosis in paracortical areas (hematoxylin-eosin, original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Lymphoma

Systemic lupus erythematosus

Kikuchi-Fujimoto disease

Rosai-Dorfman disease

c

neutral

21-30

augmented_neutral_fromfemale

https://jamanetwork.com/journals/jamacardiology/fullarticle/2810393

A woman in her 90s presented to the emergency department with symptoms of fever, hemoptysis, and syncopal episodes. She had a history of breast cancer and pulmonary nodules with biopsy findings negative for metastatic disease but positive for granulomatous inflammation. Initial vital signs included blood pressure of 103/66 mm Hg, heart rate of 190 bpm, and temperature of 38.7 °C. Electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin (Figure 1). In addition to receiving intravenous amiodarone hydrochloride, she had correction of mild hypokalemia (3.1 mEq/L [reference range, 3.5-5.2 mEq/L]; to convert to mmol/L, multiply by 1.0). Successful arrhythmia termination occurred shortly thereafter, and her vital signs remained stable. Chest computed tomographic angiography excluded pulmonary embolism but showed pulmonary nodules and mediastinal lymphadenopathy that had progressed compared with her previous computed tomography. An echocardiogram showed severe RV and left ventricular (LV) systolic dysfunction with multiple areas of hypokinesis.Patient electrocardiogram showing monomorphic regular wide complex tachycardia with a left bundle branch block morphology, with a precordial transition at V3 and inferior axis suggesting right ventricular origin. What Would You Do Next?

Cardiac magnetic resonance imaging

Electrophysiology study

Genetic testing

Implantation of cardiac defibrillator

Cardiac sarcoidosis

A

Cardiac magnetic resonance imaging

The patient underwent cardiac magnetic resonance imaging, which demonstrated areas of nonischemic near-transmural late gadolinium enhancement (LGE) of the interventricular septum and epicardium to midmyocardium of the LV basal to midanterior and basal inferior walls extending to the RV walls and septal papillary muscle (Figure 2A). However, T2 mapping revealed only discrete evidence of edema of a small region of the midanterior LV wall. Taken together, these findings raised the possibility of end-stage cardiac sarcoidosis (CS).A, Cardiac magnetic resonance imaging using phase-sensitive inversion recovery with motion correction demonstrates multiple areas of subepicardial, midmyocardial, and transmural and near-transmural late gadolinium enhancement in the left ventricle (pink arrowhead) and extending to the right ventricular wall and septal papillary muscle (blue arrowhead). B, Selected matched contiguous short-axis rubidium-82 (top row) and fluorodexoyglucose F 18 (FDG) positron emission tomographic images (bottom row) demonstrate reduced perfusion in the midseptum with marked FDG uptake in the septum and inferior wall, sparing the lateral wall.Cardiac fluorodeoxyglucose F 18 (FDG) and rubidium-82 positron emission tomography (PET) for CS was obtained with a strict high-fat, low-carbohydrate diet, followed by 12 hours of fasting prior to the examination per American Society of Nuclear Cardiology recommendations.1 Because the patient was hospitalized, dietary compliance was ensured. Furthermore, FDG uptake was segmental and the LV blood pool maximum standard uptake value was only 1.1, demonstrating adequate suppression of normal myocardial glucose utilization. There was an extensive FDG uptake (Figure 2B), with maximum standard uptake value of 10.4 in the LV septum. There was also extracardiac FDG uptake in hilar and mediastinal lymph nodes and in multiple pulmonary nodules. Rubidium-82 PET showed only mildly reduced perfusion in the basal to apical septal wall.This case highlights multiple learning points in the use of multimodality imaging for evaluation of patients with CS and understanding its complex pathophysiology. First, the utility of T2 mapping for detecting myocardial edema, a potential surrogate for active inflammation, needs to be better understood, as this can be challenging and in this case underrepresented the extensive positive FDG uptake seen on cardiac PET. Despite extensive LV and RV LGE and depressed biventricular systolic function, substantial myocardial inflammation in this patient is consistent with active rather than end-stage CS. Second, determining individual patient prognosis and assessment of immunosuppression response in patients with CS using cardiac imaging remains challenging. It has been demonstrated that patients without LGE are at an extremely low risk of arrhythmic events.2,3 However, although there is increased risk of arrhythmic events in patients with cardiac involvement identified by LGE, only a fraction of these patients experience arrhythmic events. Patients with both RV and LV LGE are at elevated risk of cardiovascular events compared with patients with only LV enhancement.2-4 Last, while CS is extremely rare after 70 years of age, as the oldest patient reported in the literature was 80 years old,5 this patient presented with CS in her 90s, reminding us that CS remains on the differential diagnosis in patients with sustained ventricular arrythmias regardless of age.Heart failure guideline–directed medical treatment, oral amiodarone, and immunosuppressive therapy consisting of a high, tapering dose of prednisone with mycophenolate mofetil were started. The patient remained stable with no more arrythmias. After shared decision discussions with the patient, a cardiac defibrillator was not implanted given the patient’s age and out of respect for her wishes. She will undergo follow-up FDG-PET to monitor her response to therapy and disease activity.

Cardiology

A woman in her 90s presented to the emergency department with symptoms of fever, hemoptysis, and syncopal episodes. She had a history of breast cancer and pulmonary nodules with biopsy findings negative for metastatic disease but positive for granulomatous inflammation. Initial vital signs included blood pressure of 103/66 mm Hg, heart rate of 190 bpm, and temperature of 38.7 °C. Electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin (Figure 1). In addition to receiving intravenous amiodarone hydrochloride, she had correction of mild hypokalemia (3.1 mEq/L [reference range, 3.5-5.2 mEq/L]; to convert to mmol/L, multiply by 1.0). Successful arrhythmia termination occurred shortly thereafter, and her vital signs remained stable. Chest computed tomographic angiography excluded pulmonary embolism but showed pulmonary nodules and mediastinal lymphadenopathy that had progressed compared with her previous computed tomography. An echocardiogram showed severe RV and left ventricular (LV) systolic dysfunction with multiple areas of hypokinesis.Patient electrocardiogram showing monomorphic regular wide complex tachycardia with a left bundle branch block morphology, with a precordial transition at V3 and inferior axis suggesting right ventricular origin.

what would you do next?

What would you do next?

Implantation of cardiac defibrillator

Electrophysiology study

Cardiac magnetic resonance imaging

Genetic testing

c

female

91-100

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2810393

A woman in her 90s presented to the emergency department with symptoms of fever, hemoptysis, and syncopal episodes. She had a history of breast cancer and pulmonary nodules with biopsy findings negative for metastatic disease but positive for granulomatous inflammation. Initial vital signs included blood pressure of 103/66 mm Hg, heart rate of 190 bpm, and temperature of 38.7 °C. Electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin (Figure 1). In addition to receiving intravenous amiodarone hydrochloride, she had correction of mild hypokalemia (3.1 mEq/L [reference range, 3.5-5.2 mEq/L]; to convert to mmol/L, multiply by 1.0). Successful arrhythmia termination occurred shortly thereafter, and her vital signs remained stable. Chest computed tomographic angiography excluded pulmonary embolism but showed pulmonary nodules and mediastinal lymphadenopathy that had progressed compared with her previous computed tomography. An echocardiogram showed severe RV and left ventricular (LV) systolic dysfunction with multiple areas of hypokinesis.Patient electrocardiogram showing monomorphic regular wide complex tachycardia with a left bundle branch block morphology, with a precordial transition at V3 and inferior axis suggesting right ventricular origin. What Would You Do Next?

Cardiac magnetic resonance imaging

Electrophysiology study

Genetic testing

Implantation of cardiac defibrillator

Cardiac sarcoidosis

A

Cardiac magnetic resonance imaging

The patient underwent cardiac magnetic resonance imaging, which demonstrated areas of nonischemic near-transmural late gadolinium enhancement (LGE) of the interventricular septum and epicardium to midmyocardium of the LV basal to midanterior and basal inferior walls extending to the RV walls and septal papillary muscle (Figure 2A). However, T2 mapping revealed only discrete evidence of edema of a small region of the midanterior LV wall. Taken together, these findings raised the possibility of end-stage cardiac sarcoidosis (CS).A, Cardiac magnetic resonance imaging using phase-sensitive inversion recovery with motion correction demonstrates multiple areas of subepicardial, midmyocardial, and transmural and near-transmural late gadolinium enhancement in the left ventricle (pink arrowhead) and extending to the right ventricular wall and septal papillary muscle (blue arrowhead). B, Selected matched contiguous short-axis rubidium-82 (top row) and fluorodexoyglucose F 18 (FDG) positron emission tomographic images (bottom row) demonstrate reduced perfusion in the midseptum with marked FDG uptake in the septum and inferior wall, sparing the lateral wall.Cardiac fluorodeoxyglucose F 18 (FDG) and rubidium-82 positron emission tomography (PET) for CS was obtained with a strict high-fat, low-carbohydrate diet, followed by 12 hours of fasting prior to the examination per American Society of Nuclear Cardiology recommendations.1 Because the patient was hospitalized, dietary compliance was ensured. Furthermore, FDG uptake was segmental and the LV blood pool maximum standard uptake value was only 1.1, demonstrating adequate suppression of normal myocardial glucose utilization. There was an extensive FDG uptake (Figure 2B), with maximum standard uptake value of 10.4 in the LV septum. There was also extracardiac FDG uptake in hilar and mediastinal lymph nodes and in multiple pulmonary nodules. Rubidium-82 PET showed only mildly reduced perfusion in the basal to apical septal wall.This case highlights multiple learning points in the use of multimodality imaging for evaluation of patients with CS and understanding its complex pathophysiology. First, the utility of T2 mapping for detecting myocardial edema, a potential surrogate for active inflammation, needs to be better understood, as this can be challenging and in this case underrepresented the extensive positive FDG uptake seen on cardiac PET. Despite extensive LV and RV LGE and depressed biventricular systolic function, substantial myocardial inflammation in this patient is consistent with active rather than end-stage CS. Second, determining individual patient prognosis and assessment of immunosuppression response in patients with CS using cardiac imaging remains challenging. It has been demonstrated that patients without LGE are at an extremely low risk of arrhythmic events.2,3 However, although there is increased risk of arrhythmic events in patients with cardiac involvement identified by LGE, only a fraction of these patients experience arrhythmic events. Patients with both RV and LV LGE are at elevated risk of cardiovascular events compared with patients with only LV enhancement.2-4 Last, while CS is extremely rare after 70 years of age, as the oldest patient reported in the literature was 80 years old,5 this patient presented with CS in her 90s, reminding us that CS remains on the differential diagnosis in patients with sustained ventricular arrythmias regardless of age.Heart failure guideline–directed medical treatment, oral amiodarone, and immunosuppressive therapy consisting of a high, tapering dose of prednisone with mycophenolate mofetil were started. The patient remained stable with no more arrythmias. After shared decision discussions with the patient, a cardiac defibrillator was not implanted given the patient’s age and out of respect for her wishes. She will undergo follow-up FDG-PET to monitor her response to therapy and disease activity.

Cardiology

A man in him 90s presented to the emergency department with symptoms of fever, hemoptysis, and syncopal episodes. He had a history of breast cancer and pulmonary nodules with biopsy findings negative for metastatic disease but positive for granulomatous inflammation. Initial vital signs included blood pressure of 103/66 mm Hg, heart rate of 190 bpm, and temperature of 38.7 °C. Electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin (Figure 1). In addition to receiving intravenous amiodarone hydrochloride, he had correction of mild hypokalemia (3.1 mEq/L [reference range, 3.5-5.2 mEq/L]; to convert to mmol/L, multiply by 1.0). Successful arrhythmia termination occurred shortly thereafter, and him vital signs remained stable. Chest computed tomographic angiography excluded pulmonary embolism but showed pulmonary nodules and mediastinal lymphadenopathy that had progressed compared with him previous computed tomography. An echocardiogram showed severe RV and left ventricular (LV) systolic dysfunction with multiple areas of hypokinesis.Man electrocardiogram showing monomorphic regular wide complex tachycardia with a left bundle branch block morphology, with a precordial transition at V3 and inferior axis suggesting right ventricular origin.

what would you do next?

What would you do next?

Implantation of cardiac defibrillator

Electrophysiology study

Cardiac magnetic resonance imaging

Genetic testing

c

male

91-100

augmented_male_fromfemale

https://jamanetwork.com/journals/jamacardiology/fullarticle/2810393

A woman in her 90s presented to the emergency department with symptoms of fever, hemoptysis, and syncopal episodes. She had a history of breast cancer and pulmonary nodules with biopsy findings negative for metastatic disease but positive for granulomatous inflammation. Initial vital signs included blood pressure of 103/66 mm Hg, heart rate of 190 bpm, and temperature of 38.7 °C. Electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin (Figure 1). In addition to receiving intravenous amiodarone hydrochloride, she had correction of mild hypokalemia (3.1 mEq/L [reference range, 3.5-5.2 mEq/L]; to convert to mmol/L, multiply by 1.0). Successful arrhythmia termination occurred shortly thereafter, and her vital signs remained stable. Chest computed tomographic angiography excluded pulmonary embolism but showed pulmonary nodules and mediastinal lymphadenopathy that had progressed compared with her previous computed tomography. An echocardiogram showed severe RV and left ventricular (LV) systolic dysfunction with multiple areas of hypokinesis.Patient electrocardiogram showing monomorphic regular wide complex tachycardia with a left bundle branch block morphology, with a precordial transition at V3 and inferior axis suggesting right ventricular origin. What Would You Do Next?

Cardiac magnetic resonance imaging

Electrophysiology study

Genetic testing

Implantation of cardiac defibrillator

Cardiac sarcoidosis

A

Cardiac magnetic resonance imaging

The patient underwent cardiac magnetic resonance imaging, which demonstrated areas of nonischemic near-transmural late gadolinium enhancement (LGE) of the interventricular septum and epicardium to midmyocardium of the LV basal to midanterior and basal inferior walls extending to the RV walls and septal papillary muscle (Figure 2A). However, T2 mapping revealed only discrete evidence of edema of a small region of the midanterior LV wall. Taken together, these findings raised the possibility of end-stage cardiac sarcoidosis (CS).A, Cardiac magnetic resonance imaging using phase-sensitive inversion recovery with motion correction demonstrates multiple areas of subepicardial, midmyocardial, and transmural and near-transmural late gadolinium enhancement in the left ventricle (pink arrowhead) and extending to the right ventricular wall and septal papillary muscle (blue arrowhead). B, Selected matched contiguous short-axis rubidium-82 (top row) and fluorodexoyglucose F 18 (FDG) positron emission tomographic images (bottom row) demonstrate reduced perfusion in the midseptum with marked FDG uptake in the septum and inferior wall, sparing the lateral wall.Cardiac fluorodeoxyglucose F 18 (FDG) and rubidium-82 positron emission tomography (PET) for CS was obtained with a strict high-fat, low-carbohydrate diet, followed by 12 hours of fasting prior to the examination per American Society of Nuclear Cardiology recommendations.1 Because the patient was hospitalized, dietary compliance was ensured. Furthermore, FDG uptake was segmental and the LV blood pool maximum standard uptake value was only 1.1, demonstrating adequate suppression of normal myocardial glucose utilization. There was an extensive FDG uptake (Figure 2B), with maximum standard uptake value of 10.4 in the LV septum. There was also extracardiac FDG uptake in hilar and mediastinal lymph nodes and in multiple pulmonary nodules. Rubidium-82 PET showed only mildly reduced perfusion in the basal to apical septal wall.This case highlights multiple learning points in the use of multimodality imaging for evaluation of patients with CS and understanding its complex pathophysiology. First, the utility of T2 mapping for detecting myocardial edema, a potential surrogate for active inflammation, needs to be better understood, as this can be challenging and in this case underrepresented the extensive positive FDG uptake seen on cardiac PET. Despite extensive LV and RV LGE and depressed biventricular systolic function, substantial myocardial inflammation in this patient is consistent with active rather than end-stage CS. Second, determining individual patient prognosis and assessment of immunosuppression response in patients with CS using cardiac imaging remains challenging. It has been demonstrated that patients without LGE are at an extremely low risk of arrhythmic events.2,3 However, although there is increased risk of arrhythmic events in patients with cardiac involvement identified by LGE, only a fraction of these patients experience arrhythmic events. Patients with both RV and LV LGE are at elevated risk of cardiovascular events compared with patients with only LV enhancement.2-4 Last, while CS is extremely rare after 70 years of age, as the oldest patient reported in the literature was 80 years old,5 this patient presented with CS in her 90s, reminding us that CS remains on the differential diagnosis in patients with sustained ventricular arrythmias regardless of age.Heart failure guideline–directed medical treatment, oral amiodarone, and immunosuppressive therapy consisting of a high, tapering dose of prednisone with mycophenolate mofetil were started. The patient remained stable with no more arrythmias. After shared decision discussions with the patient, a cardiac defibrillator was not implanted given the patient’s age and out of respect for her wishes. She will undergo follow-up FDG-PET to monitor her response to therapy and disease activity.

Cardiology

A patient in them 90s presented to the emergency department with symptoms of fever, hemoptysis, and syncopal episodes. They had a history of breast cancer and pulmonary nodules with biopsy findings negative for metastatic disease but positive for granulomatous inflammation. Initial vital signs included blood pressure of 103/66 mm Hg, heart rate of 190 bpm, and temperature of 38.7 °C. Electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin (Figure 1). In addition to receiving intravenous amiodarone hydrochloride, they had correction of mild hypokalemia (3.1 mEq/L [reference range, 3.5-5.2 mEq/L]; to convert to mmol/L, multiply by 1.0). Successful arrhythmia termination occurred shortly thereafter, and them vital signs remained stable. Chest computed tomographic angiography excluded pulmonary embolism but showed pulmonary nodules and mediastinal lymphadenopathy that had progressed compared with them previous computed tomography. An echocardiogram showed severe RV and left ventricular (LV) systolic dysfunction with multiple areas of hypokinesis.Patient electrocardiogram showing monomorphic regular wide complex tachycardia with a left bundle branch block morphology, with a precordial transition at V3 and inferior axis suggesting right ventricular origin.

what would you do next?

What would you do next?

Implantation of cardiac defibrillator

Electrophysiology study

Cardiac magnetic resonance imaging

Genetic testing

c

neutral

91-100

augmented_neutral_fromfemale

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2810455

A 27-year-old woman presented to her primary care physician with primary complaints of headaches and visual-spatial difficulties when driving at night. In addition, the patient described a progressively enlarging lesion on her left scalp, which she had initially noted in high school. She denied any overlying loss of hair, sharp pain, or bleeding from the scalp lesion, and she only reported pain with prolonged pressure. On her scalp examination, a 7-cm ill-defined spongy and pulsatile mass was noted with an overlying gray patch of hair. Magnetic resonance imaging (MRI) of the brain/orbit was initially performed (Figure, A and B), which demonstrated an ill-defined, diffuse, intensely enhancing scalp lesion in the left frontoparietal region with very prominent vascularity and underlying calvarial thickening. No osseous destruction or intracranial extension was present. Subsequent catheter angiography (Figure, C) confirmed the hypervascular mass, supplied via hypertrophied superficial temporal and occipital arteries with marked internal vascularity without direct involvement of the calvarium or intracranial structures. The patient underwent biopsy under general anesthesia; the specimen showed an ill-defined deep dermal/subcutaneous proliferation of spindle cells without significant nuclear pleomorphism or mitotic activity. The lesions stained positive for S100 and SOX10 immunostains.Coronal T2-weighted (A) and postcontrast T1-weighted (B) fat-saturated images show the large left T2 hyperintense scalp lesion (double arrowheads; A and B), with underlying calvarial thickening (asterisk; A and B) without invasion, prominent vascularity (single arrowhead; A), and enhancement (B). Note the preservation of the overlying skin. Catheter angiography (C) shows the hypervascular scalp lesion being supplied by hypertrophied branches arising from the left superficial temporal and occipital arteries, with marked internal vascularity (arrowheads). R indicates right. What Is Your Diagnosis?

Arteriovenous malformation of the scalp

Solitary fibrous tumor

Diffuse-type neurofibroma

Dermatofibrosarcoma protuberans

C. Diffuse-type neurofibroma

C

Diffuse-type neurofibroma

Neurofibromas, which are common in the head and neck, arise from endoneurium and connective tissues of peripheral nerve sheaths. From a morphologic and imaging perspective, there are 3 main types of neurofibromas: localized, diffuse, and plexiform.1 Diffuse neurofibromas are rare and represent less than 5% to 10% of all neurofibromas. The localized type, which is more common (>90%) and is the most well recognized and documented, is usually not a diagnostic conundrum. Plexiform neurofibromas, the other subtype, also have a pathognomonic imaging appearance and are frequently associated with neurofibromatosis 1, with findings of multiple lesions at different sites, which makes the diagnosis easier. Diffuse neurofibromas, however, are frequently solitary and are mostly sporadic, with few reported cases of associated with neurofibromatosis 1 (NF1).2 These lesions are more often seen in children and young adults. They are unusually large and frequently multispatial, with ill-defined margins, which appear to infiltrate and grow around tissues rather than invade them.On imaging, these are frequently plaquelike infiltrative lesions, unlike the more rounded or nodular appearance of localized neurofibromas, with frequent involvement of the subcutaneous/deep fascia both underlying the skin and overlying the musculature. Another characteristic is preservation of the overall morphologic features of the involved tissue space due to its unusual infiltrative pattern.2 A lesser known feature of these lesions is that many also demonstrate marked internal vascularity with prominent flow voids, arterial feeders, and draining veins, which can sometimes mimic vascular malformations.3 On MRI, these are isointense to mildly hyperintense to muscle on T1-weighted imaging and mild to markedly hyperintense on T2-weighted imaging to muscle, with marked enhancement. The lesions are usually solid without any necrotic or cystic changes, calcification, or hemorrhage.Solitary fibrous tumors (option B) (previously referred to as hemangiopericytomas) are rare mesenchymal-origin lesions, usually in older adults. On MRI, these are homogeneous lesions, with usually low to intermediate signals on both T1- and T2-weighted sequences (relative to muscle), with intense enhancement. They can be plaquelike and are frequently hypervascular, with numerous flow voids.4 Rarely, they may have a heterogeneous appearance secondary to internal hemorrhage or necrosis. They frequently mimic meningiomas when they arise intracranially.Scalp arteriovenous malformations (option A) are rare, and they present in children and young adults. On imaging, a predominant vascular lesion is identified with numerous flow voids due to its high flow state. The imaging features can be variable if there are associated abnormalities as well as other low-flow lesions, such as venous or lymphatic malformations. Vascular imaging, such as computed tomographic and magnetic resonance angiography, ultrasonography, and catheter angiography, is frequently done for both diagnosis and treatment planning.5Dermatofibrosarcoma protuberans (option D) are rare superficial lesions of the dermis, usually presenting in the third to fourth decade of life. These are locally aggressive, infiltrative masses that can arise in the head and neck, including the scalp. They present as a painless, slow-growing, nodular mass–like firm lesion. On imaging, these are markedly enhancing lesions, usually T1 hypointense and T2 hyperintense, with no vascular flow voids, underlying osseous invasion, or perineural spread.6 However, underlying calvarial thinning is seen in a few cases.Given the findings of the large scalp neurofibroma and her age, the patient was advised to undergo comprehensive genetic testing for NF1. Although NF1 is autosomal dominant and the patient had a negative family history, almost half of all individuals with NF1 are the first person in their family to have NF1 (de novo variant).7 The patient tested negative for identifiable pathogenic variants in the NF1 or SPRED1 genes, decreasing her risk of having NF1 and confirming that this was likely a sporadic neurofibroma.

General

A 27-year-old woman presented to her primary care physician with primary complaints of headaches and visual-spatial difficulties when driving at night. In addition, the patient described a progressively enlarging lesion on her left scalp, which she had initially noted in high school. She denied any overlying loss of hair, sharp pain, or bleeding from the scalp lesion, and she only reported pain with prolonged pressure. On her scalp examination, a 7-cm ill-defined spongy and pulsatile mass was noted with an overlying gray patch of hair. Magnetic resonance imaging (MRI) of the brain/orbit was initially performed (Figure, A and B), which demonstrated an ill-defined, diffuse, intensely enhancing scalp lesion in the left frontoparietal region with very prominent vascularity and underlying calvarial thickening. No osseous destruction or intracranial extension was present. Subsequent catheter angiography (Figure, C) confirmed the hypervascular mass, supplied via hypertrophied superficial temporal and occipital arteries with marked internal vascularity without direct involvement of the calvarium or intracranial structures. The patient underwent biopsy under general anesthesia; the specimen showed an ill-defined deep dermal/subcutaneous proliferation of spindle cells without significant nuclear pleomorphism or mitotic activity. The lesions stained positive for S100 and SOX10 immunostains.Coronal T2-weighted (A) and postcontrast T1-weighted (B) fat-saturated images show the large left T2 hyperintense scalp lesion (double arrowheads; A and B), with underlying calvarial thickening (asterisk; A and B) without invasion, prominent vascularity (single arrowhead; A), and enhancement (B). Note the preservation of the overlying skin. Catheter angiography (C) shows the hypervascular scalp lesion being supplied by hypertrophied branches arising from the left superficial temporal and occipital arteries, with marked internal vascularity (arrowheads). R indicates right.

what is your diagnosis?

What is your diagnosis?

Diffuse-type neurofibroma

Dermatofibrosarcoma protuberans

Solitary fibrous tumor

Arteriovenous malformation of the scalp

a

female

21-30

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2810455

A 27-year-old woman presented to her primary care physician with primary complaints of headaches and visual-spatial difficulties when driving at night. In addition, the patient described a progressively enlarging lesion on her left scalp, which she had initially noted in high school. She denied any overlying loss of hair, sharp pain, or bleeding from the scalp lesion, and she only reported pain with prolonged pressure. On her scalp examination, a 7-cm ill-defined spongy and pulsatile mass was noted with an overlying gray patch of hair. Magnetic resonance imaging (MRI) of the brain/orbit was initially performed (Figure, A and B), which demonstrated an ill-defined, diffuse, intensely enhancing scalp lesion in the left frontoparietal region with very prominent vascularity and underlying calvarial thickening. No osseous destruction or intracranial extension was present. Subsequent catheter angiography (Figure, C) confirmed the hypervascular mass, supplied via hypertrophied superficial temporal and occipital arteries with marked internal vascularity without direct involvement of the calvarium or intracranial structures. The patient underwent biopsy under general anesthesia; the specimen showed an ill-defined deep dermal/subcutaneous proliferation of spindle cells without significant nuclear pleomorphism or mitotic activity. The lesions stained positive for S100 and SOX10 immunostains.Coronal T2-weighted (A) and postcontrast T1-weighted (B) fat-saturated images show the large left T2 hyperintense scalp lesion (double arrowheads; A and B), with underlying calvarial thickening (asterisk; A and B) without invasion, prominent vascularity (single arrowhead; A), and enhancement (B). Note the preservation of the overlying skin. Catheter angiography (C) shows the hypervascular scalp lesion being supplied by hypertrophied branches arising from the left superficial temporal and occipital arteries, with marked internal vascularity (arrowheads). R indicates right. What Is Your Diagnosis?

Arteriovenous malformation of the scalp

Solitary fibrous tumor

Diffuse-type neurofibroma

Dermatofibrosarcoma protuberans

C. Diffuse-type neurofibroma

C

Diffuse-type neurofibroma

Neurofibromas, which are common in the head and neck, arise from endoneurium and connective tissues of peripheral nerve sheaths. From a morphologic and imaging perspective, there are 3 main types of neurofibromas: localized, diffuse, and plexiform.1 Diffuse neurofibromas are rare and represent less than 5% to 10% of all neurofibromas. The localized type, which is more common (>90%) and is the most well recognized and documented, is usually not a diagnostic conundrum. Plexiform neurofibromas, the other subtype, also have a pathognomonic imaging appearance and are frequently associated with neurofibromatosis 1, with findings of multiple lesions at different sites, which makes the diagnosis easier. Diffuse neurofibromas, however, are frequently solitary and are mostly sporadic, with few reported cases of associated with neurofibromatosis 1 (NF1).2 These lesions are more often seen in children and young adults. They are unusually large and frequently multispatial, with ill-defined margins, which appear to infiltrate and grow around tissues rather than invade them.On imaging, these are frequently plaquelike infiltrative lesions, unlike the more rounded or nodular appearance of localized neurofibromas, with frequent involvement of the subcutaneous/deep fascia both underlying the skin and overlying the musculature. Another characteristic is preservation of the overall morphologic features of the involved tissue space due to its unusual infiltrative pattern.2 A lesser known feature of these lesions is that many also demonstrate marked internal vascularity with prominent flow voids, arterial feeders, and draining veins, which can sometimes mimic vascular malformations.3 On MRI, these are isointense to mildly hyperintense to muscle on T1-weighted imaging and mild to markedly hyperintense on T2-weighted imaging to muscle, with marked enhancement. The lesions are usually solid without any necrotic or cystic changes, calcification, or hemorrhage.Solitary fibrous tumors (option B) (previously referred to as hemangiopericytomas) are rare mesenchymal-origin lesions, usually in older adults. On MRI, these are homogeneous lesions, with usually low to intermediate signals on both T1- and T2-weighted sequences (relative to muscle), with intense enhancement. They can be plaquelike and are frequently hypervascular, with numerous flow voids.4 Rarely, they may have a heterogeneous appearance secondary to internal hemorrhage or necrosis. They frequently mimic meningiomas when they arise intracranially.Scalp arteriovenous malformations (option A) are rare, and they present in children and young adults. On imaging, a predominant vascular lesion is identified with numerous flow voids due to its high flow state. The imaging features can be variable if there are associated abnormalities as well as other low-flow lesions, such as venous or lymphatic malformations. Vascular imaging, such as computed tomographic and magnetic resonance angiography, ultrasonography, and catheter angiography, is frequently done for both diagnosis and treatment planning.5Dermatofibrosarcoma protuberans (option D) are rare superficial lesions of the dermis, usually presenting in the third to fourth decade of life. These are locally aggressive, infiltrative masses that can arise in the head and neck, including the scalp. They present as a painless, slow-growing, nodular mass–like firm lesion. On imaging, these are markedly enhancing lesions, usually T1 hypointense and T2 hyperintense, with no vascular flow voids, underlying osseous invasion, or perineural spread.6 However, underlying calvarial thinning is seen in a few cases.Given the findings of the large scalp neurofibroma and her age, the patient was advised to undergo comprehensive genetic testing for NF1. Although NF1 is autosomal dominant and the patient had a negative family history, almost half of all individuals with NF1 are the first person in their family to have NF1 (de novo variant).7 The patient tested negative for identifiable pathogenic variants in the NF1 or SPRED1 genes, decreasing her risk of having NF1 and confirming that this was likely a sporadic neurofibroma.

General

A 27-year-old man presented to him primary care physician with primary complaints of headaches and visual-spatial difficulties when driving at night. In addition, the man described a progressively enlarging lesion on him left scalp, which he had initially noted in high school. He denied any overlying loss of hair, sharp pain, or bleeding from the scalp lesion, and he only reported pain with prolonged pressure. On him scalp examination, a 7-cm ill-defined spongy and pulsatile mass was noted with an overlying gray patch of hair. Magnetic resonance imaging (MRI) of the brain/orbit was initially performed (Figure, A and B), which demonstrated an ill-defined, diffuse, intensely enhancing scalp lesion in the left frontoparietal region with very prominent vascularity and underlying calvarial thickening. No osseous destruction or intracranial extension was present. Subsequent catheter angiography (Figure, C) confirmed the hypervascular mass, supplied via hypertrophied superficial temporal and occipital arteries with marked internal vascularity without direct involvement of the calvarium or intracranial structures. The man underwent biopsy under general anesthesia; the specimen showed an ill-defined deep dermal/subcutaneous proliferation of spindle cells without significant nuclear pleomorphism or mitotic activity. The lesions stained positive for S100 and SOX10 immunostains.Coronal T2-weighted (A) and postcontrast T1-weighted (B) fat-saturated images show the large left T2 hyperintense scalp lesion (double arrowheads; A and B), with underlying calvarial thickening (asterisk; A and B) without invasion, prominent vascularity (single arrowhead; A), and enhancement (B). Note the preservation of the overlying skin. Catheter angiography (C) shows the hypervascular scalp lesion being supplied by hypertrophied branches arising from the left superficial temporal and occipital arteries, with marked internal vascularity (arrowheads). R indicates right.

what is your diagnosis?

What is your diagnosis?

Diffuse-type neurofibroma

Dermatofibrosarcoma protuberans

Solitary fibrous tumor

Arteriovenous malformation of the scalp

a

male

21-30

augmented_male_fromfemale

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2810455

A 27-year-old woman presented to her primary care physician with primary complaints of headaches and visual-spatial difficulties when driving at night. In addition, the patient described a progressively enlarging lesion on her left scalp, which she had initially noted in high school. She denied any overlying loss of hair, sharp pain, or bleeding from the scalp lesion, and she only reported pain with prolonged pressure. On her scalp examination, a 7-cm ill-defined spongy and pulsatile mass was noted with an overlying gray patch of hair. Magnetic resonance imaging (MRI) of the brain/orbit was initially performed (Figure, A and B), which demonstrated an ill-defined, diffuse, intensely enhancing scalp lesion in the left frontoparietal region with very prominent vascularity and underlying calvarial thickening. No osseous destruction or intracranial extension was present. Subsequent catheter angiography (Figure, C) confirmed the hypervascular mass, supplied via hypertrophied superficial temporal and occipital arteries with marked internal vascularity without direct involvement of the calvarium or intracranial structures. The patient underwent biopsy under general anesthesia; the specimen showed an ill-defined deep dermal/subcutaneous proliferation of spindle cells without significant nuclear pleomorphism or mitotic activity. The lesions stained positive for S100 and SOX10 immunostains.Coronal T2-weighted (A) and postcontrast T1-weighted (B) fat-saturated images show the large left T2 hyperintense scalp lesion (double arrowheads; A and B), with underlying calvarial thickening (asterisk; A and B) without invasion, prominent vascularity (single arrowhead; A), and enhancement (B). Note the preservation of the overlying skin. Catheter angiography (C) shows the hypervascular scalp lesion being supplied by hypertrophied branches arising from the left superficial temporal and occipital arteries, with marked internal vascularity (arrowheads). R indicates right. What Is Your Diagnosis?

Arteriovenous malformation of the scalp

Solitary fibrous tumor

Diffuse-type neurofibroma

Dermatofibrosarcoma protuberans

C. Diffuse-type neurofibroma

C

Diffuse-type neurofibroma

Neurofibromas, which are common in the head and neck, arise from endoneurium and connective tissues of peripheral nerve sheaths. From a morphologic and imaging perspective, there are 3 main types of neurofibromas: localized, diffuse, and plexiform.1 Diffuse neurofibromas are rare and represent less than 5% to 10% of all neurofibromas. The localized type, which is more common (>90%) and is the most well recognized and documented, is usually not a diagnostic conundrum. Plexiform neurofibromas, the other subtype, also have a pathognomonic imaging appearance and are frequently associated with neurofibromatosis 1, with findings of multiple lesions at different sites, which makes the diagnosis easier. Diffuse neurofibromas, however, are frequently solitary and are mostly sporadic, with few reported cases of associated with neurofibromatosis 1 (NF1).2 These lesions are more often seen in children and young adults. They are unusually large and frequently multispatial, with ill-defined margins, which appear to infiltrate and grow around tissues rather than invade them.On imaging, these are frequently plaquelike infiltrative lesions, unlike the more rounded or nodular appearance of localized neurofibromas, with frequent involvement of the subcutaneous/deep fascia both underlying the skin and overlying the musculature. Another characteristic is preservation of the overall morphologic features of the involved tissue space due to its unusual infiltrative pattern.2 A lesser known feature of these lesions is that many also demonstrate marked internal vascularity with prominent flow voids, arterial feeders, and draining veins, which can sometimes mimic vascular malformations.3 On MRI, these are isointense to mildly hyperintense to muscle on T1-weighted imaging and mild to markedly hyperintense on T2-weighted imaging to muscle, with marked enhancement. The lesions are usually solid without any necrotic or cystic changes, calcification, or hemorrhage.Solitary fibrous tumors (option B) (previously referred to as hemangiopericytomas) are rare mesenchymal-origin lesions, usually in older adults. On MRI, these are homogeneous lesions, with usually low to intermediate signals on both T1- and T2-weighted sequences (relative to muscle), with intense enhancement. They can be plaquelike and are frequently hypervascular, with numerous flow voids.4 Rarely, they may have a heterogeneous appearance secondary to internal hemorrhage or necrosis. They frequently mimic meningiomas when they arise intracranially.Scalp arteriovenous malformations (option A) are rare, and they present in children and young adults. On imaging, a predominant vascular lesion is identified with numerous flow voids due to its high flow state. The imaging features can be variable if there are associated abnormalities as well as other low-flow lesions, such as venous or lymphatic malformations. Vascular imaging, such as computed tomographic and magnetic resonance angiography, ultrasonography, and catheter angiography, is frequently done for both diagnosis and treatment planning.5Dermatofibrosarcoma protuberans (option D) are rare superficial lesions of the dermis, usually presenting in the third to fourth decade of life. These are locally aggressive, infiltrative masses that can arise in the head and neck, including the scalp. They present as a painless, slow-growing, nodular mass–like firm lesion. On imaging, these are markedly enhancing lesions, usually T1 hypointense and T2 hyperintense, with no vascular flow voids, underlying osseous invasion, or perineural spread.6 However, underlying calvarial thinning is seen in a few cases.Given the findings of the large scalp neurofibroma and her age, the patient was advised to undergo comprehensive genetic testing for NF1. Although NF1 is autosomal dominant and the patient had a negative family history, almost half of all individuals with NF1 are the first person in their family to have NF1 (de novo variant).7 The patient tested negative for identifiable pathogenic variants in the NF1 or SPRED1 genes, decreasing her risk of having NF1 and confirming that this was likely a sporadic neurofibroma.

General

A 27-year-old patient presented to them primary care physician with primary complaints of headaches and visual-spatial difficulties when driving at night. In addition, the patient described a progressively enlarging lesion on them left scalp, which they had initially noted in high school. They denied any overlying loss of hair, sharp pain, or bleeding from the scalp lesion, and they only reported pain with prolonged pressure. On them scalp examination, a 7-cm ill-defined spongy and pulsatile mass was noted with an overlying gray patch of hair. Magnetic resonance imaging (MRI) of the brain/orbit was initially performed (Figure, A and B), which demonstrated an ill-defined, diffuse, intensely enhancing scalp lesion in the left frontoparietal region with very prominent vascularity and underlying calvarial thickening. No osseous destruction or intracranial extension was present. Subsequent catheter angiography (Figure, C) confirmed the hypervascular mass, supplied via hypertrophied superficial temporal and occipital arteries with marked internal vascularity without direct involvement of the calvarium or intracranial structures. The patient underwent biopsy under general anesthesia; the specimen showed an ill-defined deep dermal/subcutaneous proliferation of spindle cells without significant nuclear pleomorphism or mitotic activity. The lesions stained positive for S100 and SOX10 immunostains.Coronal T2-weighted (A) and postcontrast T1-weighted (B) fat-saturated images show the large left T2 hyperintense scalp lesion (double arrowheads; A and B), with underlying calvarial thickening (asterisk; A and B) without invasion, prominent vascularity (single arrowhead; A), and enhancement (B). Note the preservation of the overlying skin. Catheter angiography (C) shows the hypervascular scalp lesion being supplied by hypertrophied branches arising from the left superficial temporal and occipital arteries, with marked internal vascularity (arrowheads). R indicates right.

what is your diagnosis?

What is your diagnosis?

Diffuse-type neurofibroma

Dermatofibrosarcoma protuberans

Solitary fibrous tumor

Arteriovenous malformation of the scalp

a

neutral

21-30

augmented_neutral_fromfemale

https://jamanetwork.com/journals/jamadermatology/fullarticle/2810452

A woman in her 30s presented for evaluation of asymptomatic erythematous scaly plaques over the face and proximal extremities. The lesions started as an erythematous papule on the face, which had progressed to larger plaques within 10 years. There was involvement of the upper respiratory tract, causing palatal perforation and stridor, necessitating a tracheostomy a year ago. In addition, there was history of wheezing and breathlessness. There was no history of preceding trauma, fever, malaise, joint pain, cough, epistaxis, hemoptysis, or hematuria.Examination revealed multiple well-defined brown erythematous scaly plaques with central scarring measuring 2 × 1 to 8 × 7 cm on the face, arm, and thighs. The patient also had saddle nose deformity, perforation of the hard palate, and necrotic plaques on the ear, causing destruction of ear cartilage (Figure, A and B). There was cervical lymphadenopathy: multiple, nontender, discrete nodes, ranging from 1.5 to 2 cm without any surface changes. The results of sensory examination and peripheral nerve examination were within normal limits. Respiratory examination and chest radiography results were normal. Hemogram showed anemia (hemoglobin, 10.1 g/dL [to convert to g/L, multiply by 10.0]); the results of a kidney function test, a liver function test, a fasting blood glucose test, and routine urinalysis were within normal limits. Serologic analysis results for HIV-1/2, antinuclear antibody, and antineutrophil cytoplasmic antibodies were negative. Punch skin biopsy was obtained for histopathologic analysis and culture (Figure, C).A, Multiple well-defined brown erythematous scaly plaques with central scarring, saddle nose deformity, and necrotic lesions on the ear with loss of ear cartilage. B, Perforation of the hard palate. C, Infiltrate of foamy histiocytes and pigmented yeasts without multiaxial septation (Fontana-Masson). What Is Your Diagnosis?

Chromoblastomycosis

Hyalohyphomycosis

Blastomycosis

Phaeohyphomycosis

D. Phaeohyphomycosis

D

Phaeohyphomycosis

Histopathologic results showed pseudoepitheliomatous hyperplasia, parakeratosis, dense dermal infiltrate of histiocytes, foamy histiocytes, neutrophils, and multinucleate giant cells along with pigmented hyphae. Fungal skin culture showed black yeastlike colonies characteristic of Exophiala spinifera species. Based on clinical presentation, histopathologic analysis, and fungal culture, the diagnosis of phaeohyphomycosis was made. The patient will be treated with intravenous amphotericin B, followed by itraconazole.Phaeohyphomycosis is a rare subcutaneous mycosis caused by dematiaceous fungi found in soil, wood, and decomposing vegetation. The disease, caused by dematiaceous fungi, is classified into 2 types based on fungal forms in the tissue: phaeohyphomycosis (presence of yeasts and hyphae) and chromoblastomycosis (muriform bodies). The literal meaning of phaeohyphomycosis is dark fungus with hyphae. The pigment melanin in the fungus is a virulence factor that inhibits phagocytosis by scavenging free radicals produced by the host. The common etiological agents are Exophiala, Aureobasidium, Cladosporium, Alternaria, Phialophora, Wangiella, and Curvularia.1 Phaeohyphomycosis can affect skin, subcutaneous tissue, paranasal sinuses, and, rarely, the central nervous system. Commonly, it presents as asymptomatic cystic swelling on exposed areas, usually after traumatic inoculation involving the hands, feet, and legs. Facial involvement is uncommon and can extend to involve the upper respiratory tract, causing perforation of the palate and destruction of the nasal bridge, leading to mutilation and disfigurement.2-4 Other rare presentations include verrucous plaques, erythematous papules, and noduloulcerative lesions. The diagnosis can be confirmed by demonstration of pigmented septate hyphae with occasional globose swelling on histopathologic analysis and fungal culture. Panfungal real-time polymerase chain reaction is an emerging tool in the diagnosis of phaeohyphomycosis. Treatment with azole antifungal agents (itraconazole, posaconazole, or voriconazole) is the mainstay of treatment. Other treatment options include amphotericin B, terbinafine, flucytosine, and griseofulvin along with physical modalities, such as excision, heat therapy, and cryotherapy.5The common deep mycoses that can cause mutilation include chromoblastomycosis, hyalohyphomycosis, blastomycosis, and phaeohyphomycosis. Both chromoblastomycosis and phaeohyphomycosis are caused by dematiaceous fungi. Chromoblastomycosis (option A) is commonly caused by Fonsecaea pedrosoi, Fonsecaea monophora, and Cladophialophora carrionii and usually presents with localized, verrucous, hyperkeratotic, irregular plaque on distal extremities with scarring.6 Hyalohyphomycosis (option B) is a rare opportunistic fungal infection caused by various fungi, which produce nonpigmented septate hyphae. It has myriad presentations, which include erythematous macules, papules, vesicles, indurated verrucous plaques, necrotic ulcers, and discharging sinus.7 Blastomycosis (option C) is a suppurative fungal infection caused by Blastomyces dermatitidis, endemic in the Ohio and Mississippi River valleys, the Great Lakes, and the Saint Lawrence River. It presents with papulopustular lesions, violaceous nodules, plaques, abscesses, ulcers, and verrucous or crusted lesions on exposed body parts.8 All these infections can have systemic involvement. Chromoblastomycosis involves lungs, lymph nodes, and bone, and hyalohyphomycosis primarily affects paranasal sinuses and lungs. Blastomycosis involves lymph nodes, bone, prostate, and testis, and phaeohyphomycosis commonly involves lungs and heart.All the differential diagnoses show suppurative granuloma on histopathologic analysis; the establishment of the respective fungal form helps in confirming the diagnosis. Chromoblastomycosis is characterized by thick-walled, multicellular, globe-shaped, cigar-colored inclusion bodies with multiaxial septation called sclerotic bodies (Medlar bodies).6 Hyphae in cross-sections in the index case resembled Medlar bodies, and the absence of septation was a clue indicating phaeohyphomycosis.7 Hyalohyphomycosis is characterized by nonpigmented septate hyphae, and culture helps in confirming the diagnosis.8 Large (8-15 μm) thick-walled yeast cells, prominent broad-based budding, and centrally retracted cytoplasm help in the diagnosis of blastomycosis.9Although many clinical differential diagnoses were considered in the case presented, histopathologic analysis and culture played decisive roles in arriving at a diagnosis of phaeohyphomycosis. This case highlights the importance of recognition of rare presentation of deep mycosis and the value of histopathologic analysis and fungal cultures in establishing the right diagnosis.

Dermatology

A woman in her 30s presented for evaluation of asymptomatic erythematous scaly plaques over the face and proximal extremities. The lesions started as an erythematous papule on the face, which had progressed to larger plaques within 10 years. There was involvement of the upper respiratory tract, causing palatal perforation and stridor, necessitating a tracheostomy a year ago. In addition, there was history of wheezing and breathlessness. There was no history of preceding trauma, fever, malaise, joint pain, cough, epistaxis, hemoptysis, or hematuria.Examination revealed multiple well-defined brown erythematous scaly plaques with central scarring measuring 2 × 1 to 8 × 7 cm on the face, arm, and thighs. The patient also had saddle nose deformity, perforation of the hard palate, and necrotic plaques on the ear, causing destruction of ear cartilage (Figure, A and B). There was cervical lymphadenopathy: multiple, nontender, discrete nodes, ranging from 1.5 to 2 cm without any surface changes. The results of sensory examination and peripheral nerve examination were within normal limits. Respiratory examination and chest radiography results were normal. Hemogram showed anemia (hemoglobin, 10.1 g/dL [to convert to g/L, multiply by 10.0]); the results of a kidney function test, a liver function test, a fasting blood glucose test, and routine urinalysis were within normal limits. Serologic analysis results for HIV-1/2, antinuclear antibody, and antineutrophil cytoplasmic antibodies were negative. Punch skin biopsy was obtained for histopathologic analysis and culture (Figure, C).A, Multiple well-defined brown erythematous scaly plaques with central scarring, saddle nose deformity, and necrotic lesions on the ear with loss of ear cartilage. B, Perforation of the hard palate. C, Infiltrate of foamy histiocytes and pigmented yeasts without multiaxial septation (Fontana-Masson).

what is your diagnosis?

What is your diagnosis?

Blastomycosis

Phaeohyphomycosis

Hyalohyphomycosis

Chromoblastomycosis

b

female

31-40

original